@article{10.1117/1.NPh.11.2.024210,
	author = {Eric Klein and Sophie Marsh and Jordan Becker and Mark Andermann and Maria Lehtinen and Christopher  I. Moore},
	title = {{BioLuminescent OptoGenetics in the choroid plexus: integrated opto- and chemogenetic control in vivo}},
	volume = {11},
	journal = {Neurophotonics},
	number = {2},
	publisher = {SPIE},
	pages = {024210},
	abstract = {SignificanceThe choroid plexus (ChP) epithelial network displays diverse dynamics, including propagating calcium waves and individuated fluctuations in single cells. These rapid events underscore the possibility that ChP dynamics may reflect behaviorally relevant and clinically important changes in information processing and signaling. Optogenetic and chemogenetic tools provide spatiotemporally precise and sustained approaches for testing such dynamics in vivo. Here, we describe the feasibility of a novel combined opto- and chemogenetic tool, BioLuminescent-OptoGenetics (BL-OG), for the ChP in vivo. In the “LuMinOpsin” (LMO) BL-OG strategy, a luciferase is tethered to an adjacent optogenetic element. This molecule allows chemogenetic activation when the opsin is driven by light produced through luciferase binding a small molecule (luciferin) or by conventional optogenetic light sources and BL-OG report of activation through light production.AimTo test the viability of BL-OG/LMO for ChP control.ApproachUsing transgenic and Cre-directed targeting to the ChP, we expressed LMO3 (a Gaussia luciferase-VChR1 fusion), a highly effective construct in neural systems. In mice expressing LMO3 in ChP, we directly imaged BL light production following multiple routes of coelenterazine (CTZ: luciferin) administration using an implanted cannula system. We also used home-cage videography with Deep LabCut analysis to test for any impact of repeated CTZ administration on basic health and behavioral indices.ResultsMultiple routes of CTZ administration drove BL photon production, including intracerebroventricular, intravenous, and intraperitoneal injection. Intravenous administration resulted in fast “flash” kinetics that diminished in seconds to minutes, and intraperitoneal administration resulted in slow rising activity that sustained hours. Mice showed no consistent impact of 1 week of intraperitoneal CTZ administration on weight, drinking, motor behavior, or sleep/wake cycles.ConclusionsBL-OG/LMO provides unique advantages for testing the role of ChP dynamics in biological processes.},
	keywords = {BioLuminescent, optogenetic, chemogenetic, dynamics, behavior, Optogenetics, In vivo imaging, Bioluminescence, Animals, Neurophotonics, Molecules, Modulation, Video, Signal processing, Skull},
	year = {2024},
	doi = {10.1117/1.NPh.11.2.024210},
	URL = {https://doi.org/10.1117/1.NPh.11.2.024210}
}

SignificanceThe choroid plexus (ChP) epithelial network displays diverse dynamics, including propagating calcium waves and individuated fluctuations in single cells. These rapid events underscore the possibility that ChP dynamics may reflect behaviorally relevant and clinically important changes in information processing and signaling. Optogenetic and chemogenetic tools provide spatiotemporally precise and sustained approaches for testing such dynamics in vivo. Here, we describe the feasibility of a novel combined opto- and chemogenetic tool, BioLuminescent-OptoGenetics (BL-OG), for the ChP in vivo. In the “LuMinOpsin” (LMO) BL-OG strategy, a luciferase is tethered to an adjacent optogenetic element. This molecule allows chemogenetic activation when the opsin is driven by light produced through luciferase binding a small molecule (luciferin) or by conventional optogenetic light sources and BL-OG report of activation through light production.AimTo test the viability of BL-OG/LMO for ChP control.ApproachUsing transgenic and Cre-directed targeting to the ChP, we expressed LMO3 (a Gaussia luciferase-VChR1 fusion), a highly effective construct in neural systems. In mice expressing LMO3 in ChP, we directly imaged BL light production following multiple routes of coelenterazine (CTZ: luciferin) administration using an implanted cannula system. We also used home-cage videography with Deep LabCut analysis to test for any impact of repeated CTZ administration on basic health and behavioral indices.ResultsMultiple routes of CTZ administration drove BL photon production, including intracerebroventricular, intravenous, and intraperitoneal injection. Intravenous administration resulted in fast “flash” kinetics that diminished in seconds to minutes, and intraperitoneal administration resulted in slow rising activity that sustained hours. Mice showed no consistent impact of 1 week of intraperitoneal CTZ administration on weight, drinking, motor behavior, or sleep/wake cycles.ConclusionsBL-OG/LMO provides unique advantages for testing the role of ChP dynamics in biological processes.

@article{celinskis_toward_2024,
	title = {Toward a brighter constellation: multiorgan neuroimaging of neural and vascular dynamics in the spinal cord and brain},
	volume = {11},
	issn = {2329-423X},
	shorttitle = {Toward a brighter constellation},
	url = {https://www.spiedigitallibrary.org/journals/neurophotonics/volume-11/issue-02/024209/Toward-a-brighter-constellation--multiorgan-neuroimaging-of-neural-and/10.1117/1.NPh.11.2.024209.full},
	doi = {10.1117/1.NPh.11.2.024209},
	abstract = { SIGNIFICANCE: Pain comprises a complex interaction between motor action and somatosensation that is dependent on dynamic interactions between the brain and spinal cord. This makes understanding pain particularly challenging as it involves rich interactions between many circuits (e.g., neural and vascular) and signaling cascades throughout the body. As such, experimentation on a single region may lead to an incomplete and potentially incorrect understanding of crucial underlying mechanisms. AIM: We aimed to develop and validate tools to enable detailed and extended observation of neural and vascular activity in the brain and spinal cord. The first key set of innovations was targeted to developing novel imaging hardware that addresses the many challenges of multisite imaging. The second key set of innovations was targeted to enabling bioluminescent (BL) imaging, as this approach can address limitations of fluorescent microscopy including photobleaching, phototoxicity, and decreased resolution due to scattering of excitation signals. APPROACH: We designed 3D-printed brain and spinal cord implants to enable effective surgical implantations and optical access with wearable miniscopes or an open window (e.g., for one- or two-photon microscopy or optogenetic stimulation). We also tested the viability for BL imaging and developed a novel modified miniscope optimized for these signals (BLmini). RESULTS: We describe "universal" implants for acute and chronic simultaneous brain-spinal cord imaging and optical stimulation. We further describe successful imaging of BL signals in both foci and a new miniscope, the "BLmini," which has reduced weight, cost, and form-factor relative to standard wearable miniscopes. CONCLUSIONS: The combination of 3D-printed implants, advanced imaging tools, and bioluminescence imaging techniques offers a coalition of methods for understanding spinal cord-brain interactions. Our work has the potential for use in future research into neuropathic pain and other sensory disorders and motor behavior.}, 
	keywords = {bioluminescence, brain, fluorescence, implantable window, miniscope, multiorgan imaging, sensory processing, spinal cord, two-photon},
	number = {02},
	urldate = {2024-06-27},
	journal = {Neurophotonics},
	author = {Celinskis, Dmitrijs and Black, Christopher J. and Murphy, Jeremy and Barrios-Anderson, Adriel and Friedman, Nina G. and Shaner, Nathan C. and Saab, Carl Y. and Gomez-Ramirez, Manuel and Borton, David A. and Moore, Christopher I.},
	month = may,
	year = {2024},
}

SIGNIFICANCE: Pain comprises a complex interaction between motor action and somatosensation that is dependent on dynamic interactions between the brain and spinal cord. This makes understanding pain particularly challenging as it involves rich interactions between many circuits (e.g., neural and vascular) and signaling cascades throughout the body. As such, experimentation on a single region may lead to an incomplete and potentially incorrect understanding of crucial underlying mechanisms. AIM: We aimed to develop and validate tools to enable detailed and extended observation of neural and vascular activity in the brain and spinal cord. The first key set of innovations was targeted to developing novel imaging hardware that addresses the many challenges of multisite imaging. The second key set of innovations was targeted to enabling bioluminescent (BL) imaging, as this approach can address limitations of fluorescent microscopy including photobleaching, phototoxicity, and decreased resolution due to scattering of excitation signals. APPROACH: We designed 3D-printed brain and spinal cord implants to enable effective surgical implantations and optical access with wearable miniscopes or an open window (e.g., for one- or two-photon microscopy or optogenetic stimulation). We also tested the viability for BL imaging and developed a novel modified miniscope optimized for these signals (BLmini). RESULTS: We describe "universal" implants for acute and chronic simultaneous brain-spinal cord imaging and optical stimulation. We further describe successful imaging of BL signals in both foci and a new miniscope, the "BLmini," which has reduced weight, cost, and form-factor relative to standard wearable miniscopes. CONCLUSIONS: The combination of 3D-printed implants, advanced imaging tools, and bioluminescence imaging techniques offers a coalition of methods for understanding spinal cord-brain interactions. Our work has the potential for use in future research into neuropathic pain and other sensory disorders and motor behavior.

@article{deister_neocortical_2024,
	title = {Neocortical inhibitory imbalance predicts successful sensory detection},
	volume = {43},
	issn = {22111247},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S2211124724005618},
	doi = {10.1016/j.celrep.2024.114233},
	abstract = {Perceptual success depends on fast-spiking, parvalbumin-positive interneurons (FS/PVs). However, competing theories of optimal rate and correlation in pyramidal (PYR) firing make opposing predictions regarding the underlying FS/PV dynamics. We addressed this with population calcium imaging of FS/PVs and putative PYR neurons during threshold detection. In primary somatosensory and visual neocortex, a distinct PYR subset shows increased rate and spike-count correlations on detected trials (“hits”), while most show no rate change and decreased correlations. A larger fraction of FS/PVs predicts hits with either rate increases or decreases. Using computational modeling, we found that inhibitory imbalance, created by excitatory “feedback” and interactions between FS/PV pools, can account for the data. Rate-decreasing FS/PVs increase rate and correlation in a PYR subset, while rate-increasing FS/PVs reduce correlations and offset enhanced excitation in PYR neurons. These findings indicate that selection of informative PYR ensembles, through transient inhibitory imbalance, is a common motif of optimal neocortical processing.},
	language = {en},
	number = {7},
	urldate = {2024-06-27},
	journal = {Cell Reports},
	author = {Deister, Christopher A. and Moore, Alexander I. and Voigts, Jakob and Bechek, Sophia and Lichtin, Rebecca and Brown, Tyler C. and Moore, Christopher I.},
	month = jul,
	year = {2024},
	pages = {114233},
}

Perceptual success depends on fast-spiking, parvalbumin-positive interneurons (FS/PVs). However, competing theories of optimal rate and correlation in pyramidal (PYR) firing make opposing predictions regarding the underlying FS/PV dynamics. We addressed this with population calcium imaging of FS/PVs and putative PYR neurons during threshold detection. In primary somatosensory and visual neocortex, a distinct PYR subset shows increased rate and spike-count correlations on detected trials (“hits”), while most show no rate change and decreased correlations. A larger fraction of FS/PVs predicts hits with either rate increases or decreases. Using computational modeling, we found that inhibitory imbalance, created by excitatory “feedback” and interactions between FS/PV pools, can account for the data. Rate-decreasing FS/PVs increase rate and correlation in a PYR subset, while rate-increasing FS/PVs reduce correlations and offset enhanced excitation in PYR neurons. These findings indicate that selection of informative PYR ensembles, through transient inhibitory imbalance, is a common motif of optimal neocortical processing.

@article{slaviero_engineering_2024,
	title = {Engineering luminopsins with improved coupling efficiencies.},
	volume = {11},
	copyright = {© 2024 The Authors.},
	issn = {2329-423X 2329-4248},
	doi = {10.1117/1.NPh.11.2.024208},
	abstract = {SIGNIFICANCE: Luminopsins (LMOs) are bioluminescent-optogenetic tools with a luciferase fused to an opsin that allow bimodal control of neurons by providing  both optogenetic and chemogenetic access. Determining which design features  contribute to the efficacy of LMOs will be beneficial for further improving LMOs  for use in research. AIM: We investigated the relative impact of luciferase  brightness, opsin sensitivity, pairing of emission and absorption wavelength, and  arrangement of moieties on the function of LMOs. APPROACH: We quantified efficacy  of LMOs through whole cell patch clamp recordings in HEK293 cells by determining  coupling efficiency, the percentage of maximum LED induced photocurrent achieved  with bioluminescent activation of an opsin. We confirmed key results by  multielectrode array recordings in primary neurons. RESULTS: Luciferase  brightness and opsin sensitivity had the most impact on the efficacy of LMOs, and  N-terminal fusions of luciferases to opsins performed better than C-terminal and  multi-terminal fusions. Precise paring of luciferase emission and opsin  absorption spectra appeared to be less critical. CONCLUSIONS: Whole cell patch  clamp recordings allowed us to quantify the impact of different characteristics  of LMOs on their function. Our results suggest that coupling brighter  bioluminescent sources to more sensitive opsins will improve LMO function. As  bioluminescent activation of opsins is most likely based on Förster resonance  energy transfer, the most effective strategy for improving LMOs further will be  molecular evolution of luciferase-fluorescent protein-opsin fusions.},
	language = {eng},
	number = {2},
	journal = {Neurophotonics},
	author = {Slaviero, Ashley N. and Gorantla, Nipun and Simkins, Jacob and Crespo, Emmanuel L. and Ikefuama, Ebenezer C. and Tree, Maya O. and Prakash, Mansi and Björefeldt, Andreas and Barnett, Lauren M. and Lambert, Gerard G. and Lipscombe, Diane and Moore, Christopher I. and Shaner, Nathan C. and Hochgeschwender, Ute},
	month = apr,
	year = {2024},
	pmid = {38559366},
	pmcid = {PMC10980360},
	note = {Place: United States},
	keywords = {bioluminescence, Förster resonance energy transfer, luciferase, opsin, optogenetics, whole cell patch clamp recording},
	pages = {024208},
}

SIGNIFICANCE: Luminopsins (LMOs) are bioluminescent-optogenetic tools with a luciferase fused to an opsin that allow bimodal control of neurons by providing both optogenetic and chemogenetic access. Determining which design features contribute to the efficacy of LMOs will be beneficial for further improving LMOs for use in research. AIM: We investigated the relative impact of luciferase brightness, opsin sensitivity, pairing of emission and absorption wavelength, and arrangement of moieties on the function of LMOs. APPROACH: We quantified efficacy of LMOs through whole cell patch clamp recordings in HEK293 cells by determining coupling efficiency, the percentage of maximum LED induced photocurrent achieved with bioluminescent activation of an opsin. We confirmed key results by multielectrode array recordings in primary neurons. RESULTS: Luciferase brightness and opsin sensitivity had the most impact on the efficacy of LMOs, and N-terminal fusions of luciferases to opsins performed better than C-terminal and multi-terminal fusions. Precise paring of luciferase emission and opsin absorption spectra appeared to be less critical. CONCLUSIONS: Whole cell patch clamp recordings allowed us to quantify the impact of different characteristics of LMOs on their function. Our results suggest that coupling brighter bioluminescent sources to more sensitive opsins will improve LMO function. As bioluminescent activation of opsins is most likely based on Förster resonance energy transfer, the most effective strategy for improving LMOs further will be molecular evolution of luciferase-fluorescent protein-opsin fusions.

@article{bjorefeldt_efficient_2024,
	title = {Efficient opto- and chemogenetic control in a single molecule driven by {FRET}-modified bioluminescence.},
	volume = {11},
	copyright = {© 2024 The Authors.},
	issn = {2329-423X 2329-4248},
	doi = {10.1117/1.NPh.11.2.021005},
	abstract = {SIGNIFICANCE: Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a  single actuator molecule (a LuMinOpsin, LMO). AIM: To further enhance the utility  of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO  activation. APPROACH: We developed novel luciferases optimized for Förster  resonance energy transfer when fused to the fluorescent protein mNeonGreen,  generating bright bioluminescent (BL) emitters spectrally tuned to Volvox  Channelrhodopsin 1 (VChR1). RESULTS: A new LMO generated from this approach  (LMO7) showed significantly stronger BL-driven opsin activation compared to  previous and other new variants. We extensively benchmarked LMO7 against LMO3  (current standard) and found significantly stronger neuronal activity modulation  ex vivo and in vivo, and efficient modulation of behavior. CONCLUSIONS: We report  a robust new option for achieving multiple modes of control in a single actuator  and a promising engineering strategy for continued improvement of BL-OG.},
	language = {eng},
	number = {2},
	journal = {Neurophotonics},
	author = {Björefeldt, Andreas and Murphy, Jeremy and Crespo, Emmanuel L. and Lambert, Gerard G. and Prakash, Mansi and Ikefuama, Ebenezer C. and Friedman, Nina and Brown, Tariq M. and Lipscombe, Diane and Moore, Christopher I. and Hochgeschwender, Ute and Shaner, Nathan C.},
	month = apr,
	year = {2024},
	pmid = {38450294},
	pmcid = {PMC10917299},
	note = {Place: United States},
	keywords = {bioluminescence, Bioluminescent optogenetics, chemogenetics, luminopsin, optogenetics},
	pages = {021005},
}

SIGNIFICANCE: Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a single actuator molecule (a LuMinOpsin, LMO). AIM: To further enhance the utility of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO activation. APPROACH: We developed novel luciferases optimized for Förster resonance energy transfer when fused to the fluorescent protein mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to Volvox Channelrhodopsin 1 (VChR1). RESULTS: A new LMO generated from this approach (LMO7) showed significantly stronger BL-driven opsin activation compared to previous and other new variants. We extensively benchmarked LMO7 against LMO3 (current standard) and found significantly stronger neuronal activity modulation ex vivo and in vivo, and efficient modulation of behavior. CONCLUSIONS: We report a robust new option for achieving multiple modes of control in a single actuator and a promising engineering strategy for continued improvement of BL-OG.

@misc{celinskis_towards_2023,
	address = {United States},
	title = {Towards a {Brighter} {Constellation}: {Multi}-{Organ} {Neuroimaging} of {Neural} and {Vascular} {Dynamics} in the {Spinal} {Cord} and {Brain}.},
	doi = {10.1101/2023.12.25.573323},
	abstract = {SIGNIFICANCE: Pain is comprised of a complex interaction between motor action and somatosensation that is dependent on dynamic interactions between the brain and  spinal cord. This makes understanding pain particularly challenging as it  involves rich interactions between many circuits (e.g., neural and vascular) and  signaling cascades throughout the body. As such, experimentation on a single  region may lead to an incomplete and potentially incorrect understanding of  crucial underlying mechanisms. AIM: Here, we aimed to develop and validate new  tools to enable detailed and extended observation of neural and vascular activity  in the brain and spinal cord. The first key set of innovations were targeted to  developing novel imaging hardware that addresses the many challenges of  multi-site imaging. The second key set of innovations were targeted to enabling  bioluminescent imaging, as this approach can address limitations of fluorescent  microscopy including photobleaching, phototoxicity and decreased resolution due  to scattering of excitation signals. APPROACH: We designed 3D-printed brain and  spinal cord implants to enable effective surgical implantations and optical  access with wearable miniscopes or an open window (e.g., for one- or two-photon  microscopy or optogenetic stimulation). We also tested the viability for  bioluminescent imaging, and developed a novel modified miniscope optimized for  these signals (BLmini). RESULTS: Here, we describe novel 'universal' implants for  acute and chronic simultaneous brain-spinal cord imaging and optical stimulation.  We further describe successful imaging of bioluminescent signals in both foci,  and a new miniscope, the 'BLmini,' which has reduced weight, cost and form-factor  relative to standard wearable miniscopes. CONCLUSIONS: The combination of 3D  printed implants, advanced imaging tools, and bioluminescence imaging techniques  offers a new coalition of methods for understanding spinal cord-brain  interactions. This work has the potential for use in future research into  neuropathic pain and other sensory disorders and motor behavior.},
	language = {eng},
	author = {Celinskis, Dmitrijs and Black, Christopher J. and Murphy, Jeremy and Barrios-Anderson, Adriel and Friedman, Nina and Shaner, Nathan C. and Saab, Carl and Gomez-Ramirez, Manuel and Lipscombe, Diane and Borton, David A. and Moore, Christopher I.},
	month = dec,
	year = {2023},
	pmid = {38234789},
	pmcid = {PMC10793404},
	note = {Journal Abbreviation: bioRxiv
Pages: 2023.12.25.573323
Publication Title: bioRxiv : the preprint server for biology},
	keywords = {bioluminescence (BL), brain, fluorescence (FL), implantable window, miniscope, multi-organ imaging, sensory processing, spinal cord, two-photon},
}

SIGNIFICANCE: Pain is comprised of a complex interaction between motor action and somatosensation that is dependent on dynamic interactions between the brain and spinal cord. This makes understanding pain particularly challenging as it involves rich interactions between many circuits (e.g., neural and vascular) and signaling cascades throughout the body. As such, experimentation on a single region may lead to an incomplete and potentially incorrect understanding of crucial underlying mechanisms. AIM: Here, we aimed to develop and validate new tools to enable detailed and extended observation of neural and vascular activity in the brain and spinal cord. The first key set of innovations were targeted to developing novel imaging hardware that addresses the many challenges of multi-site imaging. The second key set of innovations were targeted to enabling bioluminescent imaging, as this approach can address limitations of fluorescent microscopy including photobleaching, phototoxicity and decreased resolution due to scattering of excitation signals. APPROACH: We designed 3D-printed brain and spinal cord implants to enable effective surgical implantations and optical access with wearable miniscopes or an open window (e.g., for one- or two-photon microscopy or optogenetic stimulation). We also tested the viability for bioluminescent imaging, and developed a novel modified miniscope optimized for these signals (BLmini). RESULTS: Here, we describe novel 'universal' implants for acute and chronic simultaneous brain-spinal cord imaging and optical stimulation. We further describe successful imaging of bioluminescent signals in both foci, and a new miniscope, the 'BLmini,' which has reduced weight, cost and form-factor relative to standard wearable miniscopes. CONCLUSIONS: The combination of 3D printed implants, advanced imaging tools, and bioluminescence imaging techniques offers a new coalition of methods for understanding spinal cord-brain interactions. This work has the potential for use in future research into neuropathic pain and other sensory disorders and motor behavior.

@misc{slaviero_engineering_2023,
	address = {United States},
	title = {Engineering luminopsins with improved coupling efficiencies.},
	doi = {10.1101/2023.11.22.568342},
	abstract = {SIGNIFICANCE: Luminopsins (LMOs) are bioluminescent-optogenetic tools with a luciferase fused to an opsin that allow bimodal control of neurons by providing  both optogenetic and chemogenetic access. Determining which design features  contribute to the efficacy of LMOs will be beneficial for further improving LMOs  for use in research. AIM: We investigated the relative impact of luciferase  brightness, opsin sensitivity, pairing of emission and absorption wavelength, and  arrangement of moieties on the function of LMOs. APPROACH: We quantified efficacy  of LMOs through whole cell patch clamp recordings in HEK293 cells by determining  coupling efficiency, the percentage of maximum LED induced photocurrent achieved  with bioluminescent activation of an opsin. We confirmed key results by  multielectrode array (MEAs) recordings in primary neurons. RESULTS: Luciferase  brightness and opsin sensitivity had the most impact on the efficacy of LMOs, and  N-terminal fusions of luciferases to opsins performed better than C-terminal and  multi-terminal fusions. Precise paring of luciferase emission and opsin  absorption spectra appeared to be less critical. CONCLUSIONS: Whole cell patch  clamp recordings allowed us to quantify the impact of different characteristics  of LMOs on their function. Our results suggest that coupling brighter  bioluminescent sources to more sensitive opsins will improve LMO function. As  bioluminescent activation of opsins is most likely based on Förster resonance  energy transfer (FRET), the most effective strategy for improving LMOs further  will be molecular evolution of luciferase-fluorescent protein-opsin fusions.},
	language = {eng},
	author = {Slaviero, Ashley and Gorantla, Nipun and Simkins, Jacob and Crespo, Emmanuel L. and Ikefuama, Ebenezer C. and Tree, Maya O. and Prakash, Mansi and Björefeldt, Andreas and Barnett, Lauren M. and Lambert, Gerard G. and Lipscombe, Diane and Moore, Christopher I. and Shaner, Nathan C. and Hochgeschwender, Ute},
	month = nov,
	year = {2023},
	pmid = {38045286},
	pmcid = {PMC10690276},
	note = {Journal Abbreviation: bioRxiv
Pages: 2023.11.22.568342
Publication Title: bioRxiv : the preprint server for biology},
	keywords = {bioluminescence, Förster resonance energy transfer, luciferase, opsin, optogenetics, whole cell patch clamp recording},
}

SIGNIFICANCE: Luminopsins (LMOs) are bioluminescent-optogenetic tools with a luciferase fused to an opsin that allow bimodal control of neurons by providing both optogenetic and chemogenetic access. Determining which design features contribute to the efficacy of LMOs will be beneficial for further improving LMOs for use in research. AIM: We investigated the relative impact of luciferase brightness, opsin sensitivity, pairing of emission and absorption wavelength, and arrangement of moieties on the function of LMOs. APPROACH: We quantified efficacy of LMOs through whole cell patch clamp recordings in HEK293 cells by determining coupling efficiency, the percentage of maximum LED induced photocurrent achieved with bioluminescent activation of an opsin. We confirmed key results by multielectrode array (MEAs) recordings in primary neurons. RESULTS: Luciferase brightness and opsin sensitivity had the most impact on the efficacy of LMOs, and N-terminal fusions of luciferases to opsins performed better than C-terminal and multi-terminal fusions. Precise paring of luciferase emission and opsin absorption spectra appeared to be less critical. CONCLUSIONS: Whole cell patch clamp recordings allowed us to quantify the impact of different characteristics of LMOs on their function. Our results suggest that coupling brighter bioluminescent sources to more sensitive opsins will improve LMO function. As bioluminescent activation of opsins is most likely based on Förster resonance energy transfer (FRET), the most effective strategy for improving LMOs further will be molecular evolution of luciferase-fluorescent protein-opsin fusions.

@misc{bjorefeldt_new_2023,
	address = {United States},
	title = {A {New} {Highly} {Efficient} {Molecule} for {Both} {Optogenetic} and {Chemogenetic} {Control} {Driven} by {FRET} {Amplification} of {BioLuminescence}.},
	doi = {10.1101/2023.06.26.545546},
	abstract = {SIGNIFICANCE: Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a  single actuator molecule (a LuMinOpsin, LMO). AIM: To further enhance the utility  of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO  activation. APPROACH: We developed novel luciferases optimized for Forster  resonance energy transfer (FRET) when fused to the fluorescent protein  mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to  Volvox Channelrhodopsin 1 (VChR1). RESULTS: A new LMO generated from this  approach (LMO7) showed significantly stronger BL-driven opsin activation compared  to previous and other new variants. We extensively benchmarked LMO7 against LMO3  (current standard), and found significantly stronger neuronal activity modulation  ex vivo and in vivo, and efficient modulation of behavior. CONCLUSIONS: We report  a robust new option for achieving multiple modes of control in a single actuator,  and a promising engineering strategy for continued improvement of BL-OG.},
	language = {eng},
	author = {Bjorefeldt, Andreas and Murphy, Jeremy and Crespo, Emmanuel L. and Lambert, Gerard G. and Prakash, Mansi and Ikefuama, Ebenezer C. and Friedman, Nina and Brown, Tariq M. and Lipscombe, Diane and Moore, Christopher I. and Hochgeschwender, Ute and Shaner, Nathan C.},
	month = dec,
	year = {2023},
	pmid = {37425735},
	pmcid = {PMC10327108},
	note = {Journal Abbreviation: bioRxiv
Pages: 2023.06.26.545546
Publication Title: bioRxiv : the preprint server for biology},
}

SIGNIFICANCE: Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a single actuator molecule (a LuMinOpsin, LMO). AIM: To further enhance the utility of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO activation. APPROACH: We developed novel luciferases optimized for Forster resonance energy transfer (FRET) when fused to the fluorescent protein mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to Volvox Channelrhodopsin 1 (VChR1). RESULTS: A new LMO generated from this approach (LMO7) showed significantly stronger BL-driven opsin activation compared to previous and other new variants. We extensively benchmarked LMO7 against LMO3 (current standard), and found significantly stronger neuronal activity modulation ex vivo and in vivo, and efficient modulation of behavior. CONCLUSIONS: We report a robust new option for achieving multiple modes of control in a single actuator, and a promising engineering strategy for continued improvement of BL-OG.

@misc{lambert_cablam_2023,
	address = {United States},
	title = {{CaBLAM}! {A} high-contrast bioluminescent {Ca}(2+) indicator derived from an engineered {Oplophorus} gracilirostris luciferase.},
	doi = {10.1101/2023.06.25.546478},
	abstract = {Ca(2+) plays many critical roles in cell physiology and biochemistry, leading researchers to develop a number of fluorescent small molecule dyes and  genetically encodable probes that optically report changes in Ca(2+)  concentrations in living cells. Though such fluorescence-based genetically  encoded Ca(2+) indicators (GECIs) have become a mainstay of modern Ca(2+) sensing  and imaging, bioluminescence-based GECIs-probes that generate light through  oxidation of a small-molecule by a luciferase or photoprotein-have several  distinct advantages over their fluorescent counterparts. Bioluminescent tags do  not photobleach, do not suffer from nonspecific autofluorescent background, and  do not lead to phototoxicity since they do not require the extremely bright  extrinsic excitation light typically required for fluorescence imaging,  especially with 2-photon microscopy. Current BL GECIs perform poorly relative to  fluorescent GECIs, producing small changes in bioluminescence intensity due to  high baseline signal at resting Ca(2+) concentrations and suboptimal Ca(2+)  affinities. Here, we describe the development of a new bioluminescent GECI,  "CaBLAM," which displays a much higher contrast (dynamic range) than previously  described bioluminescent GECIs coupled with a Ca(2+) affinity suitable for  capturing physiological changes in cytosolic Ca(2+) concentration. Derived from a  new variant of Oplophorus gracilirostris luciferase with superior in vitro  properties and a highly favorable scaffold for insertion of sensor domains,  CaBLAM allows for single-cell and subcellular resolution imaging of Ca(2+)  dynamics at high frame rates in cultured neurons. CaBLAM marks a significant  milestone in the GECI timeline, enabling Ca(2+) recordings with high spatial and  temporal resolution without perturbing cells with intense excitation light.},
	language = {eng},
	author = {Lambert, Gerard G. and Crespo, Emmanuel L. and Murphy, Jeremy and Boassa, Daniela and Luong, Selena and Celinskis, Dmitrijs and Venn, Stephanie and Hu, Junru and Sprecher, Brittany and Tree, Maya O. and Orcutt, Richard and Heydari, Daniel and Bell, Aidan B. and Torreblanca-Zanca, Albertina and Hakimi, Ali and Lipscombe, Diane and Moore, Christopher I. and Hochgeschwender, Ute and Shaner, Nathan C.},
	month = oct,
	year = {2023},
	pmid = {37425712},
	pmcid = {PMC10327125},
	note = {Journal Abbreviation: bioRxiv
Pages: 2023.06.25.546478
Publication Title: bioRxiv : the preprint server for biology},
}

Ca(2+) plays many critical roles in cell physiology and biochemistry, leading researchers to develop a number of fluorescent small molecule dyes and genetically encodable probes that optically report changes in Ca(2+) concentrations in living cells. Though such fluorescence-based genetically encoded Ca(2+) indicators (GECIs) have become a mainstay of modern Ca(2+) sensing and imaging, bioluminescence-based GECIs-probes that generate light through oxidation of a small-molecule by a luciferase or photoprotein-have several distinct advantages over their fluorescent counterparts. Bioluminescent tags do not photobleach, do not suffer from nonspecific autofluorescent background, and do not lead to phototoxicity since they do not require the extremely bright extrinsic excitation light typically required for fluorescence imaging, especially with 2-photon microscopy. Current BL GECIs perform poorly relative to fluorescent GECIs, producing small changes in bioluminescence intensity due to high baseline signal at resting Ca(2+) concentrations and suboptimal Ca(2+) affinities. Here, we describe the development of a new bioluminescent GECI, "CaBLAM," which displays a much higher contrast (dynamic range) than previously described bioluminescent GECIs coupled with a Ca(2+) affinity suitable for capturing physiological changes in cytosolic Ca(2+) concentration. Derived from a new variant of Oplophorus gracilirostris luciferase with superior in vitro properties and a highly favorable scaffold for insertion of sensor domains, CaBLAM allows for single-cell and subcellular resolution imaging of Ca(2+) dynamics at high frame rates in cultured neurons. CaBLAM marks a significant milestone in the GECI timeline, enabling Ca(2+) recordings with high spatial and temporal resolution without perturbing cells with intense excitation light.

@article{sadegh_choroid_2023,
	title = {Choroid plexus-targeted {NKCC1} overexpression to treat post-hemorrhagic hydrocephalus.},
	volume = {111},
	copyright = {Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.},
	issn = {1097-4199 0896-6273},
	doi = {10.1016/j.neuron.2023.02.020},
	abstract = {Post-hemorrhagic hydrocephalus (PHH) refers to a life-threatening accumulation of cerebrospinal fluid (CSF) that occurs following intraventricular hemorrhage  (IVH). An incomplete understanding of this variably progressive condition has  hampered the development of new therapies beyond serial neurosurgical  interventions. Here, we show a key role for the bidirectional Na-K-Cl  cotransporter, NKCC1, in the choroid plexus (ChP) to mitigate PHH. Mimicking IVH  with intraventricular blood led to increased CSF [K(+)] and triggered cytosolic  calcium activity in ChP epithelial cells, which was followed by NKCC1 activation.  ChP-targeted adeno-associated viral (AAV)-NKCC1 prevented blood-induced  ventriculomegaly and led to persistently increased CSF clearance capacity. These  data demonstrate that intraventricular blood triggered a trans-choroidal,  NKCC1-dependent CSF clearance mechanism. Inactive, phosphodeficient  AAV-NKCC1-NT51 failed to mitigate ventriculomegaly. Excessive CSF [K(+)]  fluctuations correlated with permanent shunting outcome in humans following  hemorrhagic stroke, suggesting targeted gene therapy as a potential treatment to  mitigate intracranial fluid accumulation following hemorrhage.},
	language = {eng},
	number = {10},
	journal = {Neuron},
	author = {Sadegh, Cameron and Xu, Huixin and Sutin, Jason and Fatou, Benoit and Gupta, Suhasini and Pragana, Aja and Taylor, Milo and Kalugin, Peter N. and Zawadzki, Miriam E. and Alturkistani, Osama and Shipley, Frederick B. and Dani, Neil and Fame, Ryann M. and Wurie, Zainab and Talati, Pratik and Schleicher, Riana L. and Klein, Eric M. and Zhang, Yong and Holtzman, Michael J. and Moore, Christopher I. and Lin, Pei-Yi and Patel, Aman B. and Warf, Benjamin C. and Kimberly, W. Taylor and Steen, Hanno and Andermann, Mark L. and Lehtinen, Maria K.},
	month = may,
	year = {2023},
	pmid = {36893755},
	pmcid = {PMC10198810},
	note = {Place: United States},
	keywords = {*Choroid Plexus, *Hydrocephalus/therapy, adeno-associated virus, Cerebral Hemorrhage/complications/therapy, Cerebrospinal fluid, choroid plexus, epithelial cells, gene therapy, Humans, hydrocephalus, intraventricular hemorrhage, NKCC1, ventricles},
	pages = {1591--1608.e4},
}

Post-hemorrhagic hydrocephalus (PHH) refers to a life-threatening accumulation of cerebrospinal fluid (CSF) that occurs following intraventricular hemorrhage (IVH). An incomplete understanding of this variably progressive condition has hampered the development of new therapies beyond serial neurosurgical interventions. Here, we show a key role for the bidirectional Na-K-Cl cotransporter, NKCC1, in the choroid plexus (ChP) to mitigate PHH. Mimicking IVH with intraventricular blood led to increased CSF [K(+)] and triggered cytosolic calcium activity in ChP epithelial cells, which was followed by NKCC1 activation. ChP-targeted adeno-associated viral (AAV)-NKCC1 prevented blood-induced ventriculomegaly and led to persistently increased CSF clearance capacity. These data demonstrate that intraventricular blood triggered a trans-choroidal, NKCC1-dependent CSF clearance mechanism. Inactive, phosphodeficient AAV-NKCC1-NT51 failed to mitigate ventriculomegaly. Excessive CSF [K(+)] fluctuations correlated with permanent shunting outcome in humans following hemorrhagic stroke, suggesting targeted gene therapy as a potential treatment to mitigate intracranial fluid accumulation following hemorrhage.

@article{klimas_magnify_2023,
	title = {Magnify is a universal molecular anchoring strategy for expansion microscopy.},
	volume = {41},
	copyright = {© 2023. The Author(s).},
	issn = {1546-1696 1087-0156},
	doi = {10.1038/s41587-022-01546-1},
	abstract = {Expansion microscopy enables nanoimaging with conventional microscopes by physically and isotropically magnifying preserved biological specimens embedded  in a crosslinked water-swellable hydrogel. Current expansion microscopy protocols  require prior treatment with reactive anchoring chemicals to link specific labels  and biomolecule classes to the gel. We describe a strategy called Magnify, which  uses a mechanically sturdy gel that retains nucleic acids, proteins and lipids  without the need for a separate anchoring step. Magnify expands biological  specimens up to 11 times and facilitates imaging of cells and tissues with  effectively around 25-nm resolution using a diffraction-limited objective lens of  about 280 nm on conventional optical microscopes or with around 15 nm effective  resolution if combined with super-resolution optical fluctuation imaging. We  demonstrate Magnify on a broad range of biological specimens, providing insight  into nanoscopic subcellular structures, including synaptic proteins from mouse  brain, podocyte foot processes in formalin-fixed paraffin-embedded human kidney  and defects in cilia and basal bodies in drug-treated human lung organoids.},
	language = {eng},
	number = {6},
	journal = {Nature biotechnology},
	author = {Klimas, Aleksandra and Gallagher, Brendan R. and Wijesekara, Piyumi and Fekir, Sinda and DiBernardo, Emma F. and Cheng, Zhangyu and Stolz, Donna B. and Cambi, Franca and Watkins, Simon C. and Brody, Steven L. and Horani, Amjad and Barth, Alison L. and Moore, Christopher I. and Ren, Xi and Zhao, Yongxin},
	month = jun,
	year = {2023},
	pmid = {36593399},
	pmcid = {PMC10264239},
	note = {Place: United States},
	keywords = {*Kidney, *Microscopy/methods, Animals, Humans, Mice},
	pages = {858--869},
}

Expansion microscopy enables nanoimaging with conventional microscopes by physically and isotropically magnifying preserved biological specimens embedded in a crosslinked water-swellable hydrogel. Current expansion microscopy protocols require prior treatment with reactive anchoring chemicals to link specific labels and biomolecule classes to the gel. We describe a strategy called Magnify, which uses a mechanically sturdy gel that retains nucleic acids, proteins and lipids without the need for a separate anchoring step. Magnify expands biological specimens up to 11 times and facilitates imaging of cells and tissues with effectively around 25-nm resolution using a diffraction-limited objective lens of about 280 nm on conventional optical microscopes or with around 15 nm effective resolution if combined with super-resolution optical fluctuation imaging. We demonstrate Magnify on a broad range of biological specimens, providing insight into nanoscopic subcellular structures, including synaptic proteins from mouse brain, podocyte foot processes in formalin-fixed paraffin-embedded human kidney and defects in cilia and basal bodies in drug-treated human lung organoids.

@article{klimas_nanoscale_2022,
	title = {Nanoscale {Imaging} of {Biomolecules} {Using} {Molecule} {Anchorable} {Gel}-enabled {Nanoscale} {In}-situ {Fluorescence} {Microscopy}},
	volume = {28},
	issn = {1431-9276, 1435-8115},
	url = {https://www.cambridge.org/core/product/identifier/S1431927622006298/type/journal_article},
	doi = {10.1017/S1431927622006298},
	language = {en},
	number = {S1},
	urldate = {2022-09-29},
	journal = {Microscopy and Microanalysis},
	author = {Klimas, Aleksandra and Gallagher, Brendan R. and Wijesekara, Piyumi and Fekir, Sinda and Stolz, Donna B. and Watkins, Simon and Barth, Alison L. and Moore, Christopher I. and Ren, Xi and Zhao, Yongxin},
	month = aug,
	year = {2022},
	pages = {1568--1569},
	file = {Full Text:/Users/jjallen/Zotero/storage/7UDE44WP/Klimas et al. - 2022 - Nanoscale Imaging of Biomolecules Using Molecule A.pdf:application/pdf},
}

@article{barack_call_2022,
	title = {A call for more clarity around causality in neuroscience},
	volume = {45},
	issn = {01662236},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0166223622001217},
	doi = {10.1016/j.tins.2022.06.003},
	language = {en},
	number = {9},
	urldate = {2022-09-28},
	journal = {Trends in Neurosciences},
	author = {Barack, David L. and Miller, Earl K. and Moore, Christopher I. and Packer, Adam M. and Pessoa, Luiz and Ross, Lauren N. and Rust, Nicole C.},
	month = sep,
	year = {2022},
	pages = {654--655},
}

@article{prakash_selective_2022,
	title = {Selective control of synaptically-connected circuit elements by all-optical synapses},
	volume = {5},
	issn = {2399-3642},
	url = {https://www.nature.com/articles/s42003-021-02981-7},
	doi = {10.1038/s42003-021-02981-7},
	abstract = {Abstract
            Understanding percepts, engrams and actions requires methods for selectively modulating synaptic communication between specific subsets of interconnected cells. Here, we develop an approach to control synaptically connected elements using bioluminescent light: Luciferase-generated light, originating from a presynaptic axon terminal, modulates an opsin in its postsynaptic target. Vesicular-localized luciferase is released into the synaptic cleft in response to presynaptic activity, creating a real-time Optical Synapse. Light production is under experimenter-control by introduction of the small molecule luciferin. Signal transmission across this optical synapse is temporally defined by the presence of both the luciferin and presynaptic activity. We validate synaptic Interluminescence by multi-electrode recording in cultured neurons and in mice in vivo. Interluminescence represents a powerful approach to achieve synapse-specific and activity-dependent circuit control in vivo.},
	language = {en},
	number = {1},
	urldate = {2022-01-31},
	journal = {Communications Biology},
	author = {Prakash, Mansi and Murphy, Jeremy and St Laurent, Robyn and Friedman, Nina and Crespo, Emmanuel L. and Bjorefeldt, Andreas and Pal, Akash and Bhagat, Yuvraj and Kauer, Julie A. and Shaner, Nathan C. and Lipscombe, Diane and Moore, Christopher I. and Hochgeschwender, Ute},
	month = jan,
	year = {2022},
	keywords = {BiolumHub},
	pages = {33},
	file = {Full Text:/Users/jjallen/Zotero/storage/YF4UJQSG/Prakash et al. - 2022 - Selective control of synaptically-connected circui.pdf:application/pdf},
}

Abstract Understanding percepts, engrams and actions requires methods for selectively modulating synaptic communication between specific subsets of interconnected cells. Here, we develop an approach to control synaptically connected elements using bioluminescent light: Luciferase-generated light, originating from a presynaptic axon terminal, modulates an opsin in its postsynaptic target. Vesicular-localized luciferase is released into the synaptic cleft in response to presynaptic activity, creating a real-time Optical Synapse. Light production is under experimenter-control by introduction of the small molecule luciferin. Signal transmission across this optical synapse is temporally defined by the presence of both the luciferin and presynaptic activity. We validate synaptic Interluminescence by multi-electrode recording in cultured neurons and in mice in vivo. Interluminescence represents a powerful approach to achieve synapse-specific and activity-dependent circuit control in vivo.

@article {Prakash2021.10.29.466531,
	author = {Prakash, Mansi and Murphy, Jeremy and St Laurent, Robyn and Friedman, Nina and Crespo, Emmanual and Bjorefeldt, Andreas and Pal, Akash and Bhagat, Yuvraj and Kauer, Julie A. and Shaner, Nathan and Lipscombe, Diane and Moore, Christopher and Hochgeschwender, Ute},
	title = {Selective Control of Synaptically-Connected Circuit Elements by All-Optical Synapses},
	elocation-id = {2021.10.29.466531},
	year = {2021},
	doi = {10.1101/2021.10.29.466531},
	publisher = {Cold Spring Harbor Laboratory},
	abstract = {Understanding percepts, engrams and actions requires methods for selectively modulating synaptic communication between specific subsets of interconnected cells. Here, we develop an approach to control synaptically connected elements using bioluminescent light: Luciferase-generated light, originating from a presynaptic axon terminal, modulates an opsin in its postsynaptic target. Vesicular-localized luciferase is released into the synaptic cleft in response to presynaptic activity, creating a real-time Optical Synapse. Light production is under experimenter-control by introduction of the small molecule luciferin. Signal transmission across this optical synapse is temporally defined by the presence of both the luciferin and presynaptic activity. We validate synaptic Interluminescence by multi-electrode recording in cultured neurons and in mice in vivo. Interluminescence represents a powerful approach to achieve synapse-specific and activity-dependent circuit control during behavior in vivo.Competing Interest StatementThe authors have declared no competing interest.},
	URL = {https://www.biorxiv.org/content/early/2021/11/01/2021.10.29.466531},
	eprint = {https://www.biorxiv.org/content/early/2021/11/01/2021.10.29.466531.full.pdf},
	journal = {bioRxiv}
}

Understanding percepts, engrams and actions requires methods for selectively modulating synaptic communication between specific subsets of interconnected cells. Here, we develop an approach to control synaptically connected elements using bioluminescent light: Luciferase-generated light, originating from a presynaptic axon terminal, modulates an opsin in its postsynaptic target. Vesicular-localized luciferase is released into the synaptic cleft in response to presynaptic activity, creating a real-time Optical Synapse. Light production is under experimenter-control by introduction of the small molecule luciferin. Signal transmission across this optical synapse is temporally defined by the presence of both the luciferin and presynaptic activity. We validate synaptic Interluminescence by multi-electrode recording in cultured neurons and in mice in vivo. Interluminescence represents a powerful approach to achieve synapse-specific and activity-dependent circuit control during behavior in vivo.Competing Interest StatementThe authors have declared no competing interest.

@article{CRESPO2021100667,
	title = {Bioluminescent optogenetic (BL-OG) activation of neurons during mouse postnatal brain development},
	journal = {STAR Protocols},
	volume = {2},
	number = {3},
	pages = {100667},
	year = {2021},
	issn = {2666-1667},
	doi = {https://doi.org/10.1016/j.xpro.2021.100667},
	url = {https://www.sciencedirect.com/science/article/pii/S2666166721003749},
	author = {Emmanuel L. Crespo and Mansi Prakash and Andreas Bjorefeldt and William E. Medendorp and Nathan C. Shaner and Diane Lipscombe and Christopher I. Moore and Ute Hochgeschwender},
	keywords = {Developmental biology, Microscopy, Model Organisms, Molecular Biology, Neuroscience, Biotechnology and bioengineering},
	abstract = {Summary
	Bioluminescent optogenetics (BL-OG) allows activation of photosensory proteins, such as opsins, by either fiberoptics or by administering a luciferin. BL-OG thus confers both optogenetic and chemogenetic access within the same genetically targeted neuron. This bimodality offers a powerful approach for non-invasive chemogenetic manipulation of neural activity during brain development and adult behaviors with standard optogenetic spatiotemporal precision. We detail protocols for bioluminescent stimulation of neurons in postnatally developing brain and its validation through bioluminescence imaging and electrophysiological recording in mice. For complete information on the use and execution of this protocol, please refer to Medendorp et al. (2021).}
}

Summary Bioluminescent optogenetics (BL-OG) allows activation of photosensory proteins, such as opsins, by either fiberoptics or by administering a luciferin. BL-OG thus confers both optogenetic and chemogenetic access within the same genetically targeted neuron. This bimodality offers a powerful approach for non-invasive chemogenetic manipulation of neural activity during brain development and adult behaviors with standard optogenetic spatiotemporal precision. We detail protocols for bioluminescent stimulation of neurons in postnatally developing brain and its validation through bioluminescence imaging and electrophysiological recording in mice. For complete information on the use and execution of this protocol, please refer to Medendorp et al. (2021).

@article{hamid_wave-like_nodate,
	title = {Wave-like dopamine dynamics as a mechanism for spatiotemporal credit assignment},
	issn = {0092-8674},
	url = {https://doi.org/10.1016/j.cell.2021.03.046},
	doi = {10.1016/j.cell.2021.03.046},
	abstract = {Significant evidence supports the view that dopamine shapes learning by encoding reward prediction errors. However, it is unknown whether striatal targets receive tailored dopamine dynamics based on regional functional specialization. Here, we report wave-like spatiotemporal activity patterns in dopamine axons and release across the dorsal striatum. These waves switch between activational motifs and organize dopamine transients into localized clusters within functionally related striatal subregions. Notably, wave trajectories were tailored to task demands, propagating from dorsomedial to dorsolateral striatum when rewards are contingent on animal behavior and in the opponent direction when rewards are independent of behavioral responses. We propose a computational architecture in which striatal dopamine waves are sculpted by inference about agency and provide a mechanism to direct credit assignment to specialized striatal subregions. Supporting model predictions, dorsomedial dopamine activity during reward-pursuit signaled the extent of instrumental control and interacted with reward waves to predict future behavioral adjustments.},
	journal = {Cell},
	author = {Hamid, Arif A. and Frank, Michael J. and Moore, Christopher I.},
	note = {Publisher: Elsevier},
	annote = {doi: 10.1016/j.cell.2021.03.046},
	year = {2021}
}

Significant evidence supports the view that dopamine shapes learning by encoding reward prediction errors. However, it is unknown whether striatal targets receive tailored dopamine dynamics based on regional functional specialization. Here, we report wave-like spatiotemporal activity patterns in dopamine axons and release across the dorsal striatum. These waves switch between activational motifs and organize dopamine transients into localized clusters within functionally related striatal subregions. Notably, wave trajectories were tailored to task demands, propagating from dorsomedial to dorsolateral striatum when rewards are contingent on animal behavior and in the opponent direction when rewards are independent of behavioral responses. We propose a computational architecture in which striatal dopamine waves are sculpted by inference about agency and provide a mechanism to direct credit assignment to specialized striatal subregions. Supporting model predictions, dorsomedial dopamine activity during reward-pursuit signaled the extent of instrumental control and interacted with reward waves to predict future behavioral adjustments.

@article{MEDENDORP2021102157,
	title = {Selective postnatal excitation of neocortical pyramidal neurons results in distinctive behavioral and circuit deficits in adulthood},
	journal = {iScience},
	volume = {24},
	number = {3},
	pages = {102157},
	year = {2021},
	issn = {2589-0042},
	doi = {https://doi.org/10.1016/j.isci.2021.102157},
	url = {https://www.sciencedirect.com/science/article/pii/S2589004221001255},
	author = {William E. Medendorp and Andreas Bjorefeldt and Emmanuel L. Crespo and Mansi Prakash and Akash Pal and Madison L. Waddell and Christopher I. Moore and Ute Hochgeschwender},
	keywords = {Behavioral Neuroscience, Developmental Neuroscience, Cellular Neuroscience},
	abstract = {Summary
	In genetic and pharmacological models of neurodevelopmental disorders, and human data, neural activity is altered within the developing neocortical network. This commonality begs the question of whether early enhancement in excitation might be a common driver, across etiologies, of characteristic behaviors. We tested this concept by chemogenetically driving cortical pyramidal neurons during postnatal days 4–14. Hyperexcitation of Emx1-, but not dopamine transporter-, parvalbumin-, or Dlx5/6-expressing neurons, led to decreased social interaction and increased grooming activity in adult animals. In vivo optogenetic interrogation in adults revealed decreased baseline but increased stimulus-evoked firing rates of pyramidal neurons and impaired recruitment of inhibitory neurons. Slice recordings in adults from prefrontal cortex layer 5 pyramidal neurons revealed decreased intrinsic excitability and increased synaptic E/I ratio. Together these results support the prediction that enhanced pyramidal firing during development, in otherwise normal cortex, can selectively drive altered adult circuit function and maladaptive changes in behavior.}
}

Summary In genetic and pharmacological models of neurodevelopmental disorders, and human data, neural activity is altered within the developing neocortical network. This commonality begs the question of whether early enhancement in excitation might be a common driver, across etiologies, of characteristic behaviors. We tested this concept by chemogenetically driving cortical pyramidal neurons during postnatal days 4–14. Hyperexcitation of Emx1-, but not dopamine transporter-, parvalbumin-, or Dlx5/6-expressing neurons, led to decreased social interaction and increased grooming activity in adult animals. In vivo optogenetic interrogation in adults revealed decreased baseline but increased stimulus-evoked firing rates of pyramidal neurons and impaired recruitment of inhibitory neurons. Slice recordings in adults from prefrontal cortex layer 5 pyramidal neurons revealed decreased intrinsic excitability and increased synaptic E/I ratio. Together these results support the prediction that enhanced pyramidal firing during development, in otherwise normal cortex, can selectively drive altered adult circuit function and maladaptive changes in behavior.

@article {10.7554/eLife.48957,
	article_type = {journal},
	title = {Layer 6 ensembles can selectively regulate the behavioral impact and layer-specific representation of sensory deviants},
	author = {Voigts, Jakob and Deister, Christopher A and Moore, Christopher I},
	editor = {Colgin, Laura L and Huguenard, John R and Stanley, Garrett B and Paz, Jeanne T},
	volume = 9,
	year = 2020,
	month = {dec},
	pub_date = {2020-12-02},
	pages = {e48957},
	citation = {eLife 2020;9:e48957},
	doi = {10.7554/eLife.48957},
	url = {https://doi.org/10.7554/eLife.48957},
	abstract = {Predictive models can enhance the salience of unanticipated input. Here, we tested a key potential node in neocortical model formation in this process, layer (L) 6, using behavioral, electrophysiological and imaging methods in mouse primary somatosensory neocortex. We found that deviant stimuli enhanced tactile detection and were encoded in L2/3 neural tuning. To test the contribution of L6, we applied weak optogenetic drive that changed which L6 neurons were sensory responsive, without affecting overall firing rates in L6 or L2/3. This stimulation selectively suppressed behavioral sensitivity to deviant stimuli, without impacting baseline performance. This stimulation also eliminated deviance encoding in L2/3 but did not impair basic stimulus responses across layers. In contrast, stronger L6 drive inhibited firing and suppressed overall sensory function. These findings indicate that, despite their sparse activity, specific ensembles of stimulus-driven L6 neurons are required to form neocortical predictions, and to realize their behavioral benefit.},
	keywords = {cortex, oddball, deviant, vibrissa, prediction, layer 6},
	journal = {eLife},
	issn = {2050-084X},
	publisher = {eLife Sciences Publications, Ltd}
}

Predictive models can enhance the salience of unanticipated input. Here, we tested a key potential node in neocortical model formation in this process, layer (L) 6, using behavioral, electrophysiological and imaging methods in mouse primary somatosensory neocortex. We found that deviant stimuli enhanced tactile detection and were encoded in L2/3 neural tuning. To test the contribution of L6, we applied weak optogenetic drive that changed which L6 neurons were sensory responsive, without affecting overall firing rates in L6 or L2/3. This stimulation selectively suppressed behavioral sensitivity to deviant stimuli, without impacting baseline performance. This stimulation also eliminated deviance encoding in L2/3 but did not impair basic stimulus responses across layers. In contrast, stronger L6 drive inhibited firing and suppressed overall sensory function. These findings indicate that, despite their sparse activity, specific ensembles of stimulus-driven L6 neurons are required to form neocortical predictions, and to realize their behavioral benefit.

@article {shipley_tracking_2020,
	title = {Tracking {Calcium} {Dynamics} and {Immune} {Surveillance} at the {Choroid} {Plexus}  {Blood}-{Cerebrospinal} {Fluid} {Interface}.},
	copyright = {Copyright © 2020 Elsevier Inc. All rights reserved.},
	issn = {1097-4199 0896-6273},
	doi = {10.1016/j.neuron.2020.08.024},
	abstract = {The choroid plexus (ChP) epithelium is a source of secreted signaling factors in  cerebrospinal fluid (CSF) and a key barrier between blood and brain. Here, we  develop imaging tools to interrogate these functions in adult lateral ventricle ChP  in whole-mount explants and in awake mice. By imaging epithelial cells in intact ChP  explants, we observed calcium activity and secretory events that increased in  frequency following delivery of serotonergic agonists. Using chronic two-photon  imaging in awake mice, we observed spontaneous subcellular calcium events as well as  strong agonist-evoked calcium activation and cytoplasmic secretion into CSF.  Three-dimensional imaging of motility and mobility of multiple types of ChP immune  cells at baseline and following immune challenge or focal injury revealed a range of  surveillance and defensive behaviors. Together, these tools should help illuminate  the diverse functions of this understudied body-brain interface.},
	language = {eng},
	journal = {Neuron},
	author = {Shipley, Frederick B. and Dani, Neil and Xu, Huixin and Deister, Christopher and Cui, Jin and Head, Joshua P. and Sadegh, Cameron and Fame, Ryann M. and Shannon, Morgan L. and Flores, Vanessa I. and Kishkovich, Thomas and Jang, Emily and Klein, Eric M. and Goldey, Glenn J. and He, Kangmin and Zhang, Yong and Holtzman, Michael J. and Kirchhausen, Tomas and Wyart, Claire and Moore, Christopher I. and Andermann, Mark L. and Lehtinen, Maria K.},
	month = sep,
	year = {2020},
	pmid = {32961128},
	note = {Place: United States},
	keywords = {calcium activity, cerebrospinal fluid, choroid plexus, epithelial cells, immune cells, secretion, serotonin, two-photon imaging}
}

The choroid plexus (ChP) epithelium is a source of secreted signaling factors in cerebrospinal fluid (CSF) and a key barrier between blood and brain. Here, we develop imaging tools to interrogate these functions in adult lateral ventricle ChP in whole-mount explants and in awake mice. By imaging epithelial cells in intact ChP explants, we observed calcium activity and secretory events that increased in frequency following delivery of serotonergic agonists. Using chronic two-photon imaging in awake mice, we observed spontaneous subcellular calcium events as well as strong agonist-evoked calcium activation and cytoplasmic secretion into CSF. Three-dimensional imaging of motility and mobility of multiple types of ChP immune cells at baseline and following immune challenge or focal injury revealed a range of surveillance and defensive behaviors. Together, these tools should help illuminate the diverse functions of this understudied body-brain interface.

@article {Celinskis_miniscope_2020,
	author = {Celinskis, Dmitrijs and Friedman, Nina and Koksharov, Mikhail and Murphy, Jeremy and Gomez-Ramirez, Manuel and Borton, David and Shaner, Nathan and Hochgeschwender, Ute and Lipscombe, Diane and Moore, Christopher},
	title = {Miniaturized Devices for Bioluminescence Imaging in Freely Behaving Animals},
	elocation-id = {2020.06.15.152546},
	year = {2020},
	doi = {10.1101/2020.06.15.152546},
	publisher = {Cold Spring Harbor Laboratory},
	abstract = {Fluorescence miniature microscopy in vivo has recently proven a major advance, enabling cellular imaging in freely behaving animals. However, fluorescence imaging suffers from autofluorescence, phototoxicity, photobleaching and non-homogeneous illumination artifacts. These factors limit the quality and time course of data collection. Bioluminescence provides an alternative kind of activity-dependent light indicator. Bioluminescent calcium indicators do not require light input, instead generating photons through chemiluminescence. As such, limitations inherent to the requirement for light presentation are eliminated. Further, bioluminescent indicators also do not require excitation light optics: the removal of this component should make lighter and lower cost microscope with fewer assembly parts. While there has been significant recent progress in making brighter and faster bioluminescence indicators, parallel advances in imaging hardware have not yet been realized. A hardware challenge is that despite potentially higher signal-to-noise of bioluminescence, the signal strength is lower than that of fluorescence. An open question we address in this report is whether fluorescent miniature microscopes can be rendered sensitive enough to detect bioluminescence. We demonstrate this possibility in vitro and in vivo by implementing optimizations of the UCLA fluorescent miniscope. These optimizations yielded a miniscope (BLmini) which is 22\% lighter in weight, has 45\% fewer components, is up to 58\% less expensive, offers up to 15 times stronger signal (as dichroic filtering is not required) and is sensitive enough to capture spatiotemporal dynamics of bioluminescence in the brain with a signal-to-noise ratio of 34 dB.Competing Interest StatementThe authors have declared no competing interest.},
	URL = {https://www.biorxiv.org/content/early/2020/06/16/2020.06.15.152546},
	eprint = {https://www.biorxiv.org/content/early/2020/06/16/2020.06.15.152546.full.pdf},
	journal = {bioRxiv}
}

Fluorescence miniature microscopy in vivo has recently proven a major advance, enabling cellular imaging in freely behaving animals. However, fluorescence imaging suffers from autofluorescence, phototoxicity, photobleaching and non-homogeneous illumination artifacts. These factors limit the quality and time course of data collection. Bioluminescence provides an alternative kind of activity-dependent light indicator. Bioluminescent calcium indicators do not require light input, instead generating photons through chemiluminescence. As such, limitations inherent to the requirement for light presentation are eliminated. Further, bioluminescent indicators also do not require excitation light optics: the removal of this component should make lighter and lower cost microscope with fewer assembly parts. While there has been significant recent progress in making brighter and faster bioluminescence indicators, parallel advances in imaging hardware have not yet been realized. A hardware challenge is that despite potentially higher signal-to-noise of bioluminescence, the signal strength is lower than that of fluorescence. An open question we address in this report is whether fluorescent miniature microscopes can be rendered sensitive enough to detect bioluminescence. We demonstrate this possibility in vitro and in vivo by implementing optimizations of the UCLA fluorescent miniscope. These optimizations yielded a miniscope (BLmini) which is 22% lighter in weight, has 45% fewer components, is up to 58% less expensive, offers up to 15 times stronger signal (as dichroic filtering is not required) and is sensitive enough to capture spatiotemporal dynamics of bioluminescence in the brain with a signal-to-noise ratio of 34 dB.Competing Interest StatementThe authors have declared no competing interest.

@article{neymotin_human_2020,
	title = {Human {Neocortical} {Neurosolver} ({HNN}), a new software tool for interpreting the cellular and network origin of human {MEG}/{EEG} data},
	volume = {9},
	issn = {2050-084X},
	url = {https://elifesciences.org/articles/51214},
	doi = {10.7554/eLife.51214},
	abstract = {Magneto- and electro-encephalography (MEG/EEG) non-invasively record human brain activity with millisecond resolution providing reliable markers of healthy and disease states. Relating these macroscopic signals to underlying cellular- and circuit-level generators is a limitation that constrains using MEG/EEG to reveal novel principles of information processing or to translate findings into new therapies for neuropathology. To address this problem, we built Human Neocortical Neurosolver (HNN, https://hnn.brown.edu) software. HNN has a graphical user interface designed to help researchers and clinicians interpret the neural origins of MEG/EEG. HNN’s core is a neocortical circuit model that accounts for biophysical origins of electrical currents generating MEG/EEG. Data can be directly compared to simulated signals and parameters easily manipulated to develop/test hypotheses on a signal’s origin. Tutorials teach users to simulate commonly measured signals, including event related potentials and brain rhythms. HNN’s ability to associate signals across scales makes it a unique tool for translational neuroscience research.
          , 
            Neurons carry information in the form of electrical signals. Each of these signals is too weak to detect on its own. But the combined signals from large groups of neurons can be detected using techniques called EEG and MEG. Sensors on or near the scalp detect changes in the electrical activity of groups of neurons from one millisecond to the next. These recordings can also reveal changes in brain activity due to disease.
            But how do EEG/MEG signals relate to the activity of neural circuits? While neuroscientists can rarely record electrical activity from inside the human brain, it is much easier to do so in other animals. Computer models can then compare these recordings from animals to the signals in human EEG/MEG to infer how the activity of neural circuits is changing. But building and interpreting these models requires advanced skills in mathematics and programming, which not all researchers possess.
            Neymotin et al. have therefore developed a user-friendly software platform that can help translate human EEG/MEG recordings into circuit-level activity. Known as the Human Neocortical Neurosolver, or HNN for short, the open-source tool enables users to develop and test hypotheses on the neural origin of EEG/MEG signals. The model simulates the electrical activity of cells in the outer layers of the human brain, the neocortex. By feeding human EEG/MEG data into the model, researchers can predict patterns of circuit-level activity that might have given rise to the EEG/MEG data. The HNN software includes tutorials and example datasets for commonly measured signals, including brain rhythms. It is free to use and can be installed on all major computer platforms or run online.
            HNN will help researchers and clinicians who wish to identify the neural origins of EEG/MEG signals in the healthy or diseased brain. Likewise, it will be useful to researchers studying brain activity in animals, who want to know how their findings might relate to human EEG/MEG signals. As HNN is suitable for users without training in computational neuroscience, it offers an accessible tool for discoveries in translational neuroscience.},
	language = {en},
	urldate = {2020-03-10},
	journal = {eLife},
	author = {Neymotin, Samuel A and Daniels, Dylan S and Caldwell, Blake and McDougal, Robert A and Carnevale, Nicholas T and Jas, Mainak and Moore, Christopher I and Hines, Michael L and Hämäläinen, Matti and Jones, Stephanie R},
	month = jan,
	year = {2020},
	pages = {e51214},
	file = {Full Text:/Users/jjallen/Zotero/storage/PQF9NCP6/Neymotin et al. - 2020 - Human Neocortical Neurosolver (HNN), a new softwar.pdf:application/pdf}
}

Magneto- and electro-encephalography (MEG/EEG) non-invasively record human brain activity with millisecond resolution providing reliable markers of healthy and disease states. Relating these macroscopic signals to underlying cellular- and circuit-level generators is a limitation that constrains using MEG/EEG to reveal novel principles of information processing or to translate findings into new therapies for neuropathology. To address this problem, we built Human Neocortical Neurosolver (HNN, https://hnn.brown.edu) software. HNN has a graphical user interface designed to help researchers and clinicians interpret the neural origins of MEG/EEG. HNN’s core is a neocortical circuit model that accounts for biophysical origins of electrical currents generating MEG/EEG. Data can be directly compared to simulated signals and parameters easily manipulated to develop/test hypotheses on a signal’s origin. Tutorials teach users to simulate commonly measured signals, including event related potentials and brain rhythms. HNN’s ability to associate signals across scales makes it a unique tool for translational neuroscience research. , Neurons carry information in the form of electrical signals. Each of these signals is too weak to detect on its own. But the combined signals from large groups of neurons can be detected using techniques called EEG and MEG. Sensors on or near the scalp detect changes in the electrical activity of groups of neurons from one millisecond to the next. These recordings can also reveal changes in brain activity due to disease. But how do EEG/MEG signals relate to the activity of neural circuits? While neuroscientists can rarely record electrical activity from inside the human brain, it is much easier to do so in other animals. Computer models can then compare these recordings from animals to the signals in human EEG/MEG to infer how the activity of neural circuits is changing. But building and interpreting these models requires advanced skills in mathematics and programming, which not all researchers possess. Neymotin et al. have therefore developed a user-friendly software platform that can help translate human EEG/MEG recordings into circuit-level activity. Known as the Human Neocortical Neurosolver, or HNN for short, the open-source tool enables users to develop and test hypotheses on the neural origin of EEG/MEG signals. The model simulates the electrical activity of cells in the outer layers of the human brain, the neocortex. By feeding human EEG/MEG data into the model, researchers can predict patterns of circuit-level activity that might have given rise to the EEG/MEG data. The HNN software includes tutorials and example datasets for commonly measured signals, including brain rhythms. It is free to use and can be installed on all major computer platforms or run online. HNN will help researchers and clinicians who wish to identify the neural origins of EEG/MEG signals in the healthy or diseased brain. Likewise, it will be useful to researchers studying brain activity in animals, who want to know how their findings might relate to human EEG/MEG signals. As HNN is suitable for users without training in computational neuroscience, it offers an accessible tool for discoveries in translational neuroscience.

@article{moore_blog_2020,
	title = {{BL}‐{OG}: {BioLuminescent}‐{OptoGenetics}},
	volume = {98},
	issn = {0360-4012, 1097-4547},
	shorttitle = {{BL}‐{OG}},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/jnr.24575},
	doi = {10.1002/jnr.24575},
	language = {en},
	number = {3},
	urldate = {2020-03-12},
	journal = {Journal of Neuroscience Research},
	author = {Moore, Christopher I. and Berglund, Ken},
	month = mar,
	year = {2020},
	keywords = {BiolumHub, LMO3},
	pages = {469--470}
}

@article{chen_dysfunction_2020,
	title = {Dysfunction of cortical {GABAergic} neurons leads to sensory hyper-reactivity in a {Shank3} mouse model of {ASD}},
	issn = {1097-6256, 1546-1726},
	url = {http://www.nature.com/articles/s41593-020-0598-6},
	doi = {10.1038/s41593-020-0598-6},
	abstract = {Hyper-reactivity to sensory input is a common and debilitating symptom in individuals with autism spectrum disorders (ASD), but the neural basis underlying sensory abnormality is not completely understood. Here we examined the neural representations of sensory perception in the neocortex of a Shank3B−/− mouse model of ASD. Male and female Shank3B−/− mice were more sensitive to relatively weak tactile stimulation in a vibrissa motion detection task. In vivo population calcium imaging in vibrissa primary somatosensory cortex (vS1) revealed increased spontaneous and stimulus-evoked firing in pyramidal neurons but reduced activity in interneurons. Preferential deletion of Shank3 in vS1 inhibitory interneurons led to pyramidal neuron hyperactivity and increased stimulus sensitivity in the vibrissa motion detection task. These findings provide evidence that cortical GABAergic interneuron dysfunction plays a key role in sensory hyper-reactivity in a Shank3 mouse model of ASD and identify a potential cellular target for exploring therapeutic interventions.},
	language = {en},
	urldate = {2020-03-06},
	journal = {Nature Neuroscience},
	author = {Chen, Qian and Deister, Christopher A. and Gao, Xian and Guo, Baolin and Lynn-Jones, Taylor and Chen, Naiyan and Wells, Michael F. and Liu, Runpeng and Goard, Michael J. and Dimidschstein, Jordane and Feng, Shijing and Shi, Yiwu and Liao, Weiping and Lu, Zhonghua and Fishell, Gord and Moore, Christopher I. and Feng, Guoping},
	month = mar,
	year = {2020}
}

Hyper-reactivity to sensory input is a common and debilitating symptom in individuals with autism spectrum disorders (ASD), but the neural basis underlying sensory abnormality is not completely understood. Here we examined the neural representations of sensory perception in the neocortex of a Shank3B−/− mouse model of ASD. Male and female Shank3B−/− mice were more sensitive to relatively weak tactile stimulation in a vibrissa motion detection task. In vivo population calcium imaging in vibrissa primary somatosensory cortex (vS1) revealed increased spontaneous and stimulus-evoked firing in pyramidal neurons but reduced activity in interneurons. Preferential deletion of Shank3 in vS1 inhibitory interneurons led to pyramidal neuron hyperactivity and increased stimulus sensitivity in the vibrissa motion detection task. These findings provide evidence that cortical GABAergic interneuron dysfunction plays a key role in sensory hyper-reactivity in a Shank3 mouse model of ASD and identify a potential cellular target for exploring therapeutic interventions.

@article{shin_persistent_2019,
	title = {Persistent {Gamma} {Spiking} in {SI} {Nonsensory} {Fast} {Spiking} {Cells} {Predicts} {Perceptual} {Success}},
	volume = {103},
	issn = {08966273},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0896627319305641},
	doi = {10.1016/j.neuron.2019.06.014},
	abstract = {Gamma oscillations (30-55 Hz) are hypothesized to temporally coordinate sensory encoding, enabling perception. However, fast spiking interneurons (FS), key gamma generators, can be highly sensory responsive, as is the gamma band local field potential (LFP). How can FS-mediated gamma act as an impartial temporal reference for sensory encoding, when the sensory drive itself presumably perturbs the pre-established rhythm? Combining tetrode recording in SI barrel cortex with controlled psychophysics, we found a unique FS subtype that was not sensory responsive and spiked regularly at gamma range intervals (gamma regular nonsensory FS [grnsFS]). Successful detection was predicted by a further increase in gamma regular spiking of grnsFS, persisting from before to after sensory onset. In contrast, broadband LFP power, including gamma, negatively predicted detection and did not cohere with gamma band spiking by grnsFS. These results suggest that a distinct FS subtype mediates perceptually relevant oscillations, independent of the LFP and sensory drive.},
	language = {en},
	number = {6},
	urldate = {2020-03-10},
	journal = {Neuron},
	author = {Shin, Hyeyoung and Moore, Christopher I.},
	month = sep,
	year = {2019},
	pages = {1150--1163.e5}
}

Gamma oscillations (30-55 Hz) are hypothesized to temporally coordinate sensory encoding, enabling perception. However, fast spiking interneurons (FS), key gamma generators, can be highly sensory responsive, as is the gamma band local field potential (LFP). How can FS-mediated gamma act as an impartial temporal reference for sensory encoding, when the sensory drive itself presumably perturbs the pre-established rhythm? Combining tetrode recording in SI barrel cortex with controlled psychophysics, we found a unique FS subtype that was not sensory responsive and spiked regularly at gamma range intervals (gamma regular nonsensory FS [grnsFS]). Successful detection was predicted by a further increase in gamma regular spiking of grnsFS, persisting from before to after sensory onset. In contrast, broadband LFP power, including gamma, negatively predicted detection and did not cohere with gamma band spiking by grnsFS. These results suggest that a distinct FS subtype mediates perceptually relevant oscillations, independent of the LFP and sensory drive.

@article{gomezramirez_bioluminescentoptogenetic_2019,
	title = {The {BioLuminescent}‐{OptoGenetic} \textit{in vivo} response to coelenterazine is proportional, sensitive, and specific in neocortex},
	issn = {0360-4012, 1097-4547},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/jnr.24498},
	doi = {10.1002/jnr.24498},
	abstract = {BioLuminescent (BL) light production can modulate neural activity and behavior through co‐expressed OptoGenetic (OG) elements, an approach termed “BL‐OG.” Yet, the relationship between BL‐OG effects and bioluminescent photon emission has not been characterized in vivo. Further, the degree to which BL‐OG effects strictly depend on optogenetic mechanisms driven by bioluminescent photons is unknown. Crucial to every neuromodulation method is whether the activator shows a dynamic concentration range driving robust, selective, and nontoxic effects. We systematically tested the effects of four key components of the BL‐OG mechanism (luciferin, oxidized luciferin, luciferin vehicle, and bioluminescence), and compared these against effects induced by the Luminopsin‐3 (LMO3) BL‐OG molecule, a fusion of slow burn Gaussia luciferase (sbGLuc) and Volvox ChannelRhodopsin‐1 (VChR1). We performed combined bioluminescence imaging and electrophysiological recordings while injecting specific doses of Coelenterazine (substrate for sbGluc), Coelenteramide (CTM, the oxidized product of CTZ), or CTZ vehicle. CTZ robustly drove activity in mice expressing LMO3, with photon production proportional to firing rate. In contrast, low and moderate doses of CTZ, CTM, or vehicle did not modulate activity in mice that did not express LMO3. We also failed to find bioluminescence effects on neural activity in mice expressing an optogenetically nonsensitive LMO3 variant. We observed weak responses to the highest dose of CTZ in control mice, but these effects were significantly smaller than those observed in the LMO3 group. These results show that in neocortex in vivo, there is a large CTZ range wherein BL‐OG effects are specific to its active chemogenetic mechanism.},
	language = {en},
	urldate = {2019-09-25},
	journal = {Journal of Neuroscience Research},
	author = {Gomez‐Ramirez, Manuel and More, Alexander I. and Friedman, Nina G. and Hochgeschwender, Ute and Moore, Christopher I.},
	month = sep,
	year = {2019},
	keywords = {BiolumHub, LMO3},
	pages = {jnr.24498}
}

BioLuminescent (BL) light production can modulate neural activity and behavior through co‐expressed OptoGenetic (OG) elements, an approach termed “BL‐OG.” Yet, the relationship between BL‐OG effects and bioluminescent photon emission has not been characterized in vivo. Further, the degree to which BL‐OG effects strictly depend on optogenetic mechanisms driven by bioluminescent photons is unknown. Crucial to every neuromodulation method is whether the activator shows a dynamic concentration range driving robust, selective, and nontoxic effects. We systematically tested the effects of four key components of the BL‐OG mechanism (luciferin, oxidized luciferin, luciferin vehicle, and bioluminescence), and compared these against effects induced by the Luminopsin‐3 (LMO3) BL‐OG molecule, a fusion of slow burn Gaussia luciferase (sbGLuc) and Volvox ChannelRhodopsin‐1 (VChR1). We performed combined bioluminescence imaging and electrophysiological recordings while injecting specific doses of Coelenterazine (substrate for sbGluc), Coelenteramide (CTM, the oxidized product of CTZ), or CTZ vehicle. CTZ robustly drove activity in mice expressing LMO3, with photon production proportional to firing rate. In contrast, low and moderate doses of CTZ, CTM, or vehicle did not modulate activity in mice that did not express LMO3. We also failed to find bioluminescence effects on neural activity in mice expressing an optogenetically nonsensitive LMO3 variant. We observed weak responses to the highest dose of CTZ in control mice, but these effects were significantly smaller than those observed in the LMO3 group. These results show that in neocortex in vivo, there is a large CTZ range wherein BL‐OG effects are specific to its active chemogenetic mechanism.

@article{sliva_prospective_2018,
	title = {A {Prospective} {Study} of the {Impact} of {Transcranial} {Alternating} {Current} {Stimulation} on {EEG} {Correlates} of {Somatosensory} {Perception}},
	volume = {9},
	issn = {1664-1078},
	url = {https://www.frontiersin.org/article/10.3389/fpsyg.2018.02117/full},
	doi = {10.3389/fpsyg.2018.02117},
	abstract = {The (8-12 Hz) neocortical alpha rhythm is associated with shifts in attention across sensory systems, and is thought to represent a sensory gating mechanism for the inhibitory control of cortical processing. The present preliminary study sought to explore whether alpha frequency transcranial alternating current stimulation (tACS) could modulate endogenous alpha power in the somatosensory system, and whether the hypothesized modulation would causally impact perception of tactile stimuli at perceptual threshold. We combined electroencephalography (EEG) with simultaneous brief and intermittent tACS applied over primary somatosensory cortex at individuals' endogenous alpha frequency during a tactile detection task (n = 12 for EEG, n = 20 for behavior). EEG-measured pre-stimulus alpha power was higher on non-perceived than perceived trials, and analogous perceptual correlates emerged in early components of the tactile evoked response. Further, baseline normalized tactile detection performance was significantly lower during alpha than sham tACS, but the effect did not last into the post-tACS time period. Pre- to post-tACS changes in alpha power were linearly dependent upon baseline state, such that alpha power tended to increase when pre-tACS alpha power was low, and decrease when it was high. However, these observations were comparable in both groups, and not associated with evidence of tACS-induced alpha power modulation. Nevertheless, the tactile stimulus evoked response potential (ERP) revealed a potentially lasting impact of alpha tACS on circuit dynamics. The post-tACS ERP was marked by the emergence of a prominent peak ∼70 ms post-stimulus, which was not discernible post-sham, or in either pre-stimulation condition. Computational neural modeling designed to simulate macroscale EEG signals supported the hypothesis that the emergence of this peak could reflect synaptic plasticity mechanisms induced by tACS. The primary lesson learned in this study, which commanded a small sample size, was that while our experimental paradigm provided some evidence of an influence of tACS on behavior and circuit dynamics, it was not sufficient to induce observable causal effects of tACS on EEG-measured alpha oscillations. We discuss limitations and suggest improvements that may help further delineate a causal influence of tACS on cortical dynamics and perception in future studies.},
	urldate = {2020-03-10},
	journal = {Frontiers in Psychology},
	author = {Sliva, Danielle D. and Black, Christopher J. and Bowary, Paul and Agrawal, Uday and Santoyo, Juan F. and Philip, Noah S. and Greenberg, Benjamin D. and Moore, Christopher I. and Jones, Stephanie R.},
	month = nov,
	year = {2018},
	pages = {2117},
	file = {Full Text:/Users/jjallen/Zotero/storage/ZX4TVKPI/Sliva et al. - 2018 - A Prospective Study of the Impact of Transcranial .pdf:application/pdf}
}

The (8-12 Hz) neocortical alpha rhythm is associated with shifts in attention across sensory systems, and is thought to represent a sensory gating mechanism for the inhibitory control of cortical processing. The present preliminary study sought to explore whether alpha frequency transcranial alternating current stimulation (tACS) could modulate endogenous alpha power in the somatosensory system, and whether the hypothesized modulation would causally impact perception of tactile stimuli at perceptual threshold. We combined electroencephalography (EEG) with simultaneous brief and intermittent tACS applied over primary somatosensory cortex at individuals' endogenous alpha frequency during a tactile detection task (n = 12 for EEG, n = 20 for behavior). EEG-measured pre-stimulus alpha power was higher on non-perceived than perceived trials, and analogous perceptual correlates emerged in early components of the tactile evoked response. Further, baseline normalized tactile detection performance was significantly lower during alpha than sham tACS, but the effect did not last into the post-tACS time period. Pre- to post-tACS changes in alpha power were linearly dependent upon baseline state, such that alpha power tended to increase when pre-tACS alpha power was low, and decrease when it was high. However, these observations were comparable in both groups, and not associated with evidence of tACS-induced alpha power modulation. Nevertheless, the tactile stimulus evoked response potential (ERP) revealed a potentially lasting impact of alpha tACS on circuit dynamics. The post-tACS ERP was marked by the emergence of a prominent peak ∼70 ms post-stimulus, which was not discernible post-sham, or in either pre-stimulation condition. Computational neural modeling designed to simulate macroscale EEG signals supported the hypothesis that the emergence of this peak could reflect synaptic plasticity mechanisms induced by tACS. The primary lesson learned in this study, which commanded a small sample size, was that while our experimental paradigm provided some evidence of an influence of tACS on behavior and circuit dynamics, it was not sufficient to induce observable causal effects of tACS on EEG-measured alpha oscillations. We discuss limitations and suggest improvements that may help further delineate a causal influence of tACS on cortical dynamics and perception in future studies.

@article{higashikubo_systematic_2018,
	title = {Systematic {Examination} of the {Impact} of {Depolarization} {Duration} on {Thalamic} {Reticular} {Nucleus} {Firing} in vivo},
	volume = {368},
	issn = {03064522},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0306452217306917},
	doi = {10.1016/j.neuroscience.2017.09.038},
	abstract = {The thalamic reticular nucleus (TRN) is optimally positioned to regulate information processing and state dynamics in dorsal thalamus. Distinct inputs depolarize TRN on multiple time scales, including thalamocortical afferents, corticothalamic 'feedback', and neuromodulation. Here, we systematically tested the concurrent and after-effects of depolarization duration on TRN firing in vivo using selective optogenetic drive. In VGAT-ChR2 mice, we isolated TRN single units (SU: N = 100 neurons) that responded at brief latency (≤5 ms) to stimulation. These units, and multi-unit activity (MUA) on corresponding electrodes, were analyzed in detail. Consistent with prior findings in relay neurons, after light cessation, burst-like events occurred in 74\% of MUA sites, and 16\% of SU. Increasing optical duration from 2 to 330 ms enhanced this burst probability, and decreased the latency to the first burst after stimulation. During stimulation, neurons demonstrated a 'plateau' firing response lasting 20-30 ms in response to light, but significant heterogeneity existed in the minimal stimuli required to drive this response. Two distinct types were evident, more sensitive 'non-linear' neurons that were driven to the plateau response by 2 or 5 ms pulses, versus 'linear' neurons that fired proportionally to optical duration, and reached the plateau with ∼20-ms optical drive. Non-linear neurons showed higher evoked firing rates and burst probability, but spontaneous rate did not differ between types. These findings provide direct predictions for TRN responses to a range of natural depolarizing inputs, and a guide for the optical control of this key structure in studies of network function and behavior.},
	language = {en},
	urldate = {2020-03-10},
	journal = {Neuroscience},
	author = {Higashikubo, Bryan and Moore, Christopher I.},
	month = jan,
	year = {2018},
	pages = {187--198}
}

The thalamic reticular nucleus (TRN) is optimally positioned to regulate information processing and state dynamics in dorsal thalamus. Distinct inputs depolarize TRN on multiple time scales, including thalamocortical afferents, corticothalamic 'feedback', and neuromodulation. Here, we systematically tested the concurrent and after-effects of depolarization duration on TRN firing in vivo using selective optogenetic drive. In VGAT-ChR2 mice, we isolated TRN single units (SU: N = 100 neurons) that responded at brief latency (≤5 ms) to stimulation. These units, and multi-unit activity (MUA) on corresponding electrodes, were analyzed in detail. Consistent with prior findings in relay neurons, after light cessation, burst-like events occurred in 74% of MUA sites, and 16% of SU. Increasing optical duration from 2 to 330 ms enhanced this burst probability, and decreased the latency to the first burst after stimulation. During stimulation, neurons demonstrated a 'plateau' firing response lasting 20-30 ms in response to light, but significant heterogeneity existed in the minimal stimuli required to drive this response. Two distinct types were evident, more sensitive 'non-linear' neurons that were driven to the plateau response by 2 or 5 ms pulses, versus 'linear' neurons that fired proportionally to optical duration, and reached the plateau with ∼20-ms optical drive. Non-linear neurons showed higher evoked firing rates and burst probability, but spontaneous rate did not differ between types. These findings provide direct predictions for TRN responses to a range of natural depolarizing inputs, and a guide for the optical control of this key structure in studies of network function and behavior.

@article{goodwill_early_2018,
	title = {Early {Life} {Stress} {Drives} {Sex}-{Selective} {Impairment} in {Reversal} {Learning} by {Affecting} {Parvalbumin} {Interneurons} in {Orbitofrontal} {Cortex} of {Mice}},
	volume = {25},
	issn = {22111247},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S221112471831756X},
	doi = {10.1016/j.celrep.2018.11.010},
	abstract = {Poverty, displacement, and parental stress represent potent sources of early life stress (ELS). Stress disproportionately affects females, who are at increased risk for stress-related pathologies associated with cognitive impairment. Mechanisms underlying stress-associated cognitive impairment and enhanced risk of females remain unknown. Here, ELS is associated with impaired rule-reversal (RR) learning in females, but not males. Impaired performance was associated with decreased expression and density of interneurons expressing parvalbumin (PV+) in orbitofrontal cortex (OFC), but not other interneuron subtypes. Optogenetic silencing of PV+ interneuron activity in OFC of control mice phenocopied RR learning deficits observed in ELS females. Localization of reversal learning deficits to PV+ interneurons in OFC was confirmed by optogenetic studies in which neurons in medial prefrontal cortex (mPFC) were silenced and associated with select deficits in rule-shift learning. Sex-, cell-, and region-specific effects show altered PV+ interneuron development can be a driver of sex differences in cognitive dysfunction.},
	language = {en},
	number = {9},
	urldate = {2020-03-10},
	journal = {Cell Reports},
	author = {Goodwill, Haley L. and Manzano-Nieves, Gabriela and LaChance, Patrick and Teramoto, Sana and Lin, Shirley and Lopez, Chelsea and Stevenson, Rachel J. and Theyel, Brian B. and Moore, Christopher I. and Connors, Barry W. and Bath, Kevin G.},
	month = nov,
	year = {2018},
	pages = {2299--2307.e4},
	file = {Full Text:/Users/jjallen/Zotero/storage/EKM3CEMJ/Goodwill et al. - 2018 - Early Life Stress Drives Sex-Selective Impairment .pdf:application/pdf}
}

Poverty, displacement, and parental stress represent potent sources of early life stress (ELS). Stress disproportionately affects females, who are at increased risk for stress-related pathologies associated with cognitive impairment. Mechanisms underlying stress-associated cognitive impairment and enhanced risk of females remain unknown. Here, ELS is associated with impaired rule-reversal (RR) learning in females, but not males. Impaired performance was associated with decreased expression and density of interneurons expressing parvalbumin (PV+) in orbitofrontal cortex (OFC), but not other interneuron subtypes. Optogenetic silencing of PV+ interneuron activity in OFC of control mice phenocopied RR learning deficits observed in ELS females. Localization of reversal learning deficits to PV+ interneurons in OFC was confirmed by optogenetic studies in which neurons in medial prefrontal cortex (mPFC) were silenced and associated with select deficits in rule-shift learning. Sex-, cell-, and region-specific effects show altered PV+ interneuron development can be a driver of sex differences in cognitive dysfunction.

@article{shin_rate_2017,
	title = {The rate of transient beta frequency events predicts behavior across tasks and species},
	volume = {6},
	issn = {2050-084X},
	url = {https://elifesciences.org/articles/29086},
	doi = {10.7554/eLife.29086},
	abstract = {Beta oscillations (15-29Hz) are among the most prominent signatures of brain activity. Beta power is predictive of healthy and abnormal behaviors, including perception, attention and motor action. In non-averaged signals, beta can emerge as transient high-power 'events'. As such, functionally relevant differences in averaged power across time and trials can reflect changes in event number, power, duration, and/or frequency span. We show that functionally relevant differences in averaged beta power in primary somatosensory neocortex reflect a difference in the number of high-power beta events per trial, i.e. event rate. Further, beta events occurring close to the stimulus were more likely to impair perception. These results are consistent across detection and attention tasks in human magnetoencephalography, and in local field potentials from mice performing a detection task. These results imply that an increased propensity of beta events predicts the failure to effectively transmit information through specific neocortical representations.},
	language = {en},
	urldate = {2020-03-10},
	journal = {eLife},
	author = {Shin, Hyeyoung and Law, Robert and Tsutsui, Shawn and Moore, Christopher I and Jones, Stephanie R},
	month = nov,
	year = {2017},
	pages = {e29086},
	file = {Full Text:/Users/jjallen/Zotero/storage/ZNJ8JFMF/Shin et al. - 2017 - The rate of transient beta frequency events predic.pdf:application/pdf}
}

Beta oscillations (15-29Hz) are among the most prominent signatures of brain activity. Beta power is predictive of healthy and abnormal behaviors, including perception, attention and motor action. In non-averaged signals, beta can emerge as transient high-power 'events'. As such, functionally relevant differences in averaged power across time and trials can reflect changes in event number, power, duration, and/or frequency span. We show that functionally relevant differences in averaged beta power in primary somatosensory neocortex reflect a difference in the number of high-power beta events per trial, i.e. event rate. Further, beta events occurring close to the stimulus were more likely to impair perception. These results are consistent across detection and attention tasks in human magnetoencephalography, and in local field potentials from mice performing a detection task. These results imply that an increased propensity of beta events predicts the failure to effectively transmit information through specific neocortical representations.

@article{leblanc_thalamic_2017,
	title = {Thalamic {Bursts} {Down}-regulate {Cortical} {Theta} and {Nociceptive} {Behavior}},
	volume = {7},
	issn = {2045-2322},
	url = {http://www.nature.com/articles/s41598-017-02753-6},
	doi = {10.1038/s41598-017-02753-6},
	abstract = {We tested the relation between pain behavior, theta (4-8 Hz) oscillations in somatosensory cortex and burst firing in thalamic neurons in vivo. Optically-induced thalamic bursts attenuated cortical theta and mechanical allodynia. It is proposed that thalamic bursts are an adaptive response to pain that de-synchronizes cortical theta and decreases sensory salience.},
	language = {en},
	number = {1},
	urldate = {2020-03-10},
	journal = {Scientific Reports},
	author = {LeBlanc, Brian W. and Cross, Brent and Smith, Kelsey A. and Roach, Catherine and Xia, Jimmy and Chao, Yu-Chieh and Levitt, Joshua and Koyama, Suguru and Moore, Christopher I. and Saab, Carl Y.},
	month = dec,
	year = {2017},
	pages = {2482},
	file = {Full Text:/Users/jjallen/Zotero/storage/QAPXWUTA/LeBlanc et al. - 2017 - Thalamic Bursts Down-regulate Cortical Theta and N.pdf:application/pdf}
}

We tested the relation between pain behavior, theta (4-8 Hz) oscillations in somatosensory cortex and burst firing in thalamic neurons in vivo. Optically-induced thalamic bursts attenuated cortical theta and mechanical allodynia. It is proposed that thalamic bursts are an adaptive response to pain that de-synchronizes cortical theta and decreases sensory salience.

@article{sherman_neural_2016,
	title = {Neural mechanisms of transient neocortical beta rhythms: {Converging} evidence from humans, computational modeling, monkeys, and mice},
	volume = {113},
	issn = {0027-8424, 1091-6490},
	shorttitle = {Neural mechanisms of transient neocortical beta rhythms},
	url = {http://www.pnas.org/lookup/doi/10.1073/pnas.1604135113},
	doi = {10.1073/pnas.1604135113},
	abstract = {Human neocortical 15–29-Hz beta oscillations are strong predictors of perceptual and motor performance. However, the mechanistic origin of beta in vivo is unknown, hindering understanding of its functional role. Combining human magnetoencephalography (MEG), computational modeling, and laminar recordings in animals, we present a new theory that accounts for the origin of spontaneous neocortical beta. In our MEG data, spontaneous beta activity from somatosensory and frontal cortex emerged as noncontinuous beta events typically lasting {\textless}150 ms with a stereotypical waveform. Computational modeling uniquely designed to infer the electrical currents underlying these signals showed that beta events could emerge from the integration of nearly synchronous bursts of excitatory synaptic drive targeting proximal and distal dendrites of pyramidal neurons, where the defining feature of a beta event was a strong distal drive that lasted one beta period (∼50 ms). This beta mechanism rigorously accounted for the beta event profiles; several other mechanisms did not. The spatial location of synaptic drive in the model to supragranular and infragranular layers was critical to the emergence of beta events and led to the prediction that beta events should be associated with a specific laminar current profile. Laminar recordings in somatosensory neocortex from anesthetized mice and awake monkeys supported these predictions, suggesting this beta mechanism is conserved across species and recording modalities. These findings make several predictions about optimal states for perceptual and motor performance and guide causal interventions to modulate beta for optimal function.},
	language = {en},
	number = {33},
	urldate = {2020-03-12},
	journal = {Proceedings of the National Academy of Sciences},
	author = {Sherman, Maxwell A. and Lee, Shane and Law, Robert and Haegens, Saskia and Thorn, Catherine A. and Hämäläinen, Matti S. and Moore, Christopher I. and Jones, Stephanie R.},
	month = aug,
	year = {2016},
	pages = {E4885--E4894},
	file = {Full Text:/Users/jjallen/Zotero/storage/EP947M8C/Sherman et al. - 2016 - Neural mechanisms of transient neocortical beta rh.pdf:application/pdf}
}

Human neocortical 15–29-Hz beta oscillations are strong predictors of perceptual and motor performance. However, the mechanistic origin of beta in vivo is unknown, hindering understanding of its functional role. Combining human magnetoencephalography (MEG), computational modeling, and laminar recordings in animals, we present a new theory that accounts for the origin of spontaneous neocortical beta. In our MEG data, spontaneous beta activity from somatosensory and frontal cortex emerged as noncontinuous beta events typically lasting \textless150 ms with a stereotypical waveform. Computational modeling uniquely designed to infer the electrical currents underlying these signals showed that beta events could emerge from the integration of nearly synchronous bursts of excitatory synaptic drive targeting proximal and distal dendrites of pyramidal neurons, where the defining feature of a beta event was a strong distal drive that lasted one beta period (∼50 ms). This beta mechanism rigorously accounted for the beta event profiles; several other mechanisms did not. The spatial location of synaptic drive in the model to supragranular and infragranular layers was critical to the emergence of beta events and led to the prediction that beta events should be associated with a specific laminar current profile. Laminar recordings in somatosensory neocortex from anesthetized mice and awake monkeys supported these predictions, suggesting this beta mechanism is conserved across species and recording modalities. These findings make several predictions about optimal states for perceptual and motor performance and guide causal interventions to modulate beta for optimal function.

@article{berglund_combined_2016,
	title = {Combined {Optogenetic} and {Chemogenetic} {Control} of {Neurons}},
	volume = {1408},
	issn = {1940-6029},
	doi = {10.1007/978-1-4939-3512-3_14},
	abstract = {Optogenetics provides an array of elements for specific biophysical control, while designer chemogenetic receptors provide a minimally invasive method to control circuits in vivo by peripheral injection. We developed a strategy for selective regulation of activity in specific cells that integrates opto- and chemogenetic approaches, and thus allows manipulation of neuronal activity over a range of spatial and temporal scales in the same experimental animal. Light-sensing molecules (opsins) are activated by biologically produced light through luciferases upon peripheral injection of a small molecule substrate. Such luminescent opsins, luminopsins, allow conventional fiber optic use of optogenetic sensors, while at the same time providing chemogenetic access to the same sensors. We describe applications of this approach in cultured neurons in vitro, in brain slices ex vivo, and in awake and anesthetized animals in vivo.},
	language = {eng},
	journal = {Methods in Molecular Biology (Clifton, N.J.)},
	author = {Berglund, Ken and Tung, Jack K. and Higashikubo, Bryan and Gross, Robert E. and Moore, Christopher I. and Hochgeschwender, Ute},
	year = {2016},
	pmid = {26965125},
	pmcid = {PMC5149414},
	keywords = {Animals, Behavior, Bioluminescence, Brain, Cell Culture Techniques, Cells, Cultured, Chemogenetics, Coelenterazine, Electrodes, Electrophysiological Phenomena, Electrophysiology, Fiber Optic Technology, HEK293 Cells, Humans, Light, Luciferase, Luciferases, Luminescence, Luminescent Agents, Luminescent Measurements, Luminopsin, Multielectrode array, Neuron, Neurons, Opsins, Optical Imaging, Optogenetics, Rats},
	pages = {207--225},
	file = {Accepted Version:/Users/jjallen/Zotero/storage/5RFL87PT/Berglund et al. - 2016 - Combined Optogenetic and Chemogenetic Control of N.pdf:application/pdf}
}

Optogenetics provides an array of elements for specific biophysical control, while designer chemogenetic receptors provide a minimally invasive method to control circuits in vivo by peripheral injection. We developed a strategy for selective regulation of activity in specific cells that integrates opto- and chemogenetic approaches, and thus allows manipulation of neuronal activity over a range of spatial and temporal scales in the same experimental animal. Light-sensing molecules (opsins) are activated by biologically produced light through luciferases upon peripheral injection of a small molecule substrate. Such luminescent opsins, luminopsins, allow conventional fiber optic use of optogenetic sensors, while at the same time providing chemogenetic access to the same sensors. We describe applications of this approach in cultured neurons in vitro, in brain slices ex vivo, and in awake and anesthetized animals in vivo.

@article{10.1117/1.NPh.2.3.031201,
	author = {Christopher I. Moore and Itamar Kahn},
	title = {{Special Section Guest Editorial: Causal Control of Biological Systems with Light}},
	volume = {2},
	journal = {Neurophotonics},
	number = {3},
	publisher = {SPIE},
	pages = {031201},
	keywords = {Optogenetics, Control systems, Neurons, Neuroscience, In vivo imaging, Brain, Molecules, Pharmacology, Receptors, In vitro testing},
	year = {2015},
	doi = {10.1117/1.NPh.2.3.031201},
	URL = {https://doi.org/10.1117/1.NPh.2.3.031201},
}

@article{badre_interactionist_2015,
	title = {Interactionist {Neuroscience}},
	volume = {88},
	issn = {08966273},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0896627315008879},
	doi = {10.1016/j.neuron.2015.10.021},
	language = {en},
	number = {5},
	urldate = {2022-09-29},
	journal = {Neuron},
	author = {Badre, David and Frank, Michael J. and Moore, Christopher I.},
	month = dec,
	year = {2015},
	pages = {855--860},
	file = {Full Text:/Users/jjallen/Zotero/storage/G4X6LG9M/Badre et al. - 2015 - Interactionist Neuroscience.pdf:application/pdf},
}

@article{sacchet_attention_2015,
	title = {Attention {Drives} {Synchronization} of {Alpha} and {Beta} {Rhythms} between {Right} {Inferior} {Frontal} and {Primary} {Sensory} {Neocortex}},
	volume = {35},
	issn = {0270-6474, 1529-2401},
	url = {http://www.jneurosci.org/cgi/doi/10.1523/JNEUROSCI.1292-14.2015},
	doi = {10.1523/JNEUROSCI.1292-14.2015},
	language = {en},
	number = {5},
	urldate = {2020-03-12},
	journal = {Journal of Neuroscience},
	author = {Sacchet, M. D. and LaPlante, R. A. and Wan, Q. and Pritchett, D. L. and Lee, A. K. C. and Hamalainen, M. and Moore, C. I. and Kerr, C. E. and Jones, S. R.},
	month = feb,
	year = {2015},
	pages = {2074--2082},
	file = {Full Text:/Users/jjallen/Zotero/storage/23TTKASV/Sacchet et al. - 2015 - Attention Drives Synchronization of Alpha and Beta.pdf:application/pdf}
}

@article{pritchett_for_2015,
	title = {For things needing your attention: the role of neocortical gamma in sensory perception},
	volume = {31},
	issn = {09594388},
	shorttitle = {For things needing your attention},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0959438815000343},
	doi = {10.1016/j.conb.2015.02.004},
	abstract = {Two general classes of hypotheses for the role for gamma oscillations in sensation are those that predict gamma facilitates signal amplification through local synchronization of a distinct ensemble, and those that predict gamma modulates fine temporal relationships between neurons to represent information. Correlative evidence has been offered for and against these hypotheses. A recent study in which gamma was optogenetically entrained by driving fast-spiking interneurons showed enhanced sensory detection of harder-to-perceive stimuli, those that benefit most from attention, in agreement with the amplification hypotheses. These findings are supported by similar studies employing less specific optogenetic patterns or single neuron stimulation, but contrast with findings based on direct optogenetic stimulation of pyramidal neurons. Key next steps for this topic are described.},
	language = {en},
	urldate = {2020-03-12},
	journal = {Current Opinion in Neurobiology},
	author = {Pritchett, Dominique L and Siegle, Joshua H and Deister, Christopher A and Moore, Christopher I},
	month = apr,
	year = {2015},
	pages = {254--263}
}

Two general classes of hypotheses for the role for gamma oscillations in sensation are those that predict gamma facilitates signal amplification through local synchronization of a distinct ensemble, and those that predict gamma modulates fine temporal relationships between neurons to represent information. Correlative evidence has been offered for and against these hypotheses. A recent study in which gamma was optogenetically entrained by driving fast-spiking interneurons showed enhanced sensory detection of harder-to-perceive stimuli, those that benefit most from attention, in agreement with the amplification hypotheses. These findings are supported by similar studies employing less specific optogenetic patterns or single neuron stimulation, but contrast with findings based on direct optogenetic stimulation of pyramidal neurons. Key next steps for this topic are described.

@article{badre_interactionist_2015,
	title = {Interactionist {Neuroscience}},
	volume = {88},
	issn = {08966273},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0896627315008879},
	doi = {10.1016/j.neuron.2015.10.021},
	abstract = {We argue that bidirectional interaction between animal and human studies is essential for understanding the human brain. The revolution in meso-scale study of circuits in non-human species provides a historical opportunity. However, to fully realize its potential requires integration with human neuroscience. We describe three strategies for successful interactionist neuroscience.},
	language = {en},
	number = {5},
	urldate = {2020-03-12},
	journal = {Neuron},
	author = {Badre, David and Frank, Michael J. and Moore, Christopher I.},
	month = dec,
	year = {2015},
	pages = {855--860},
	file = {Full Text:/Users/jjallen/Zotero/storage/FCC78HTZ/Badre et al. - 2015 - Interactionist Neuroscience.pdf:application/pdf}
}

We argue that bidirectional interaction between animal and human studies is essential for understanding the human brain. The revolution in meso-scale study of circuits in non-human species provides a historical opportunity. However, to fully realize its potential requires integration with human neuroscience. We describe three strategies for successful interactionist neuroscience.

@article{siegle_gamma-range_2014,
	title = {Gamma-range synchronization of fast-spiking interneurons can enhance detection of tactile stimuli},
	volume = {17},
	issn = {1097-6256, 1546-1726},
	url = {http://www.nature.com/articles/nn.3797},
	doi = {10.1038/nn.3797},
	abstract = {We tested the sensory impact of repeated synchronization of fast-spiking interneurons (FS), an activity pattern thought to underlie neocortical gamma oscillations. We optogenetically drove 'FS-gamma' while mice detected naturalistic vibrissal stimuli and found enhanced detection of less salient stimuli and impaired detection of more salient ones. Prior studies have predicted that the benefit of FS-gamma is generated when sensory neocortical excitation arrives in a specific temporal window 20-25 ms after FS synchronization. To systematically test this prediction, we aligned periodic tactile and optogenetic stimulation. We found that the detection of less salient stimuli was improved only when peripheral drive led to the arrival of excitation 20-25 ms after synchronization and that other temporal alignments either had no effects or impaired detection. These results provide causal evidence that FS-gamma can enhance processing of less salient stimuli, those that benefit from the allocation of attention.},
	language = {en},
	number = {10},
	urldate = {2020-03-12},
	journal = {Nature Neuroscience},
	author = {Siegle, Joshua H and Pritchett, Dominique L and Moore, Christopher I},
	month = oct,
	year = {2014},
	pages = {1371--1379},
	file = {Accepted Version:/Users/jjallen/Zotero/storage/5WIIM7WH/Siegle et al. - 2014 - Gamma-range synchronization of fast-spiking intern.pdf:application/pdf}
}

We tested the sensory impact of repeated synchronization of fast-spiking interneurons (FS), an activity pattern thought to underlie neocortical gamma oscillations. We optogenetically drove 'FS-gamma' while mice detected naturalistic vibrissal stimuli and found enhanced detection of less salient stimuli and impaired detection of more salient ones. Prior studies have predicted that the benefit of FS-gamma is generated when sensory neocortical excitation arrives in a specific temporal window 20-25 ms after FS synchronization. To systematically test this prediction, we aligned periodic tactile and optogenetic stimulation. We found that the detection of less salient stimuli was improved only when peripheral drive led to the arrival of excitation 20-25 ms after synchronization and that other temporal alignments either had no effects or impaired detection. These results provide causal evidence that FS-gamma can enhance processing of less salient stimuli, those that benefit from the allocation of attention.

@article{voigts_flexdrive_2013,
	title = {The {flexDrive}: an ultra-light implant for optical control and highly parallel chronic recording of neuronal ensembles in freely moving mice},
	volume = {7},
	issn = {1662-5137},
	shorttitle = {The {flexDrive}},
	url = {http://journal.frontiersin.org/article/10.3389/fnsys.2013.00008/abstract},
	doi = {10.3389/fnsys.2013.00008},
	abstract = {Electrophysiological recordings from ensembles of neurons in behaving mice are a central tool in the study of neural circuits. Despite the widespread use of chronic electrophysiology, the precise positioning of recording electrodes required for high-quality recordings remains a challenge, especially in behaving mice. The complexity of available drive mechanisms, combined with restrictions on implant weight tolerated by mice, limits current methods to recordings from no more than 4-8 electrodes in a single target area. We developed a highly miniaturized yet simple drive design that can be used to independently position 16 electrodes with up to 64 channels in a package that weighs {\textasciitilde}2 g. This advance over current designs is achieved by a novel spring-based drive mechanism that reduces implant weight and complexity. The device is easy to build and accommodates arbitrary spatial arrangements of electrodes. Multiple optical fibers can be integrated into the recording array and independently manipulated in depth. Thus, our novel design enables precise optogenetic control and highly parallel chronic recordings of identified single neurons throughout neural circuits in mice.},
	urldate = {2020-03-12},
	journal = {Frontiers in Systems Neuroscience},
	author = {Voigts, Jakob and Siegle, Joshua H. and Pritchett, Dominique L. and Moore, Christopher I.},
	year = {2013},
	file = {Full Text:/Users/jjallen/Zotero/storage/58FF8742/Voigts et al. - 2013 - The flexDrive an ultra-light implant for optical .pdf:application/pdf}
}

Electrophysiological recordings from ensembles of neurons in behaving mice are a central tool in the study of neural circuits. Despite the widespread use of chronic electrophysiology, the precise positioning of recording electrodes required for high-quality recordings remains a challenge, especially in behaving mice. The complexity of available drive mechanisms, combined with restrictions on implant weight tolerated by mice, limits current methods to recordings from no more than 4-8 electrodes in a single target area. We developed a highly miniaturized yet simple drive design that can be used to independently position 16 electrodes with up to 64 channels in a package that weighs ~2 g. This advance over current designs is achieved by a novel spring-based drive mechanism that reduces implant weight and complexity. The device is easy to build and accommodates arbitrary spatial arrangements of electrodes. Multiple optical fibers can be integrated into the recording array and independently manipulated in depth. Thus, our novel design enables precise optogenetic control and highly parallel chronic recordings of identified single neurons throughout neural circuits in mice.

@article{normand_temporal_2013,
	title = {Temporal and {Mosaic} {Tsc1} {Deletion} in the {Developing} {Thalamus} {Disrupts} {Thalamocortical} {Circuitry}, {Neural} {Function}, and {Behavior}},
	volume = {78},
	issn = {08966273},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0896627313002778},
	doi = {10.1016/j.neuron.2013.03.030},
	language = {en},
	number = {5},
	urldate = {2020-03-12},
	journal = {Neuron},
	author = {Normand, Elizabeth A. and Crandall, Shane R. and Thorn, Catherine A. and Murphy, Emily M. and Voelcker, Bettina and Browning, Catherine and Machan, Jason T. and Moore, Christopher I. and Connors, Barry W. and Zervas, Mark},
	month = jun,
	year = {2013},
	pages = {895--909},
	file = {Full Text:/Users/jjallen/Zotero/storage/JM5UXBBR/Normand et al. - 2013 - Temporal and Mosaic Tsc1 Deletion in the Developin.pdf:application/pdf}
}

@article{moore_neocortical_2013,
	title = {Neocortical {Correlates} of {Vibrotactile} {Detection} in {Humans}},
	volume = {25},
	issn = {0898-929X, 1530-8898},
	url = {http://www.mitpressjournals.org/doi/10.1162/jocn_a_00315},
	doi = {10.1162/jocn_a_00315},
	abstract = {This study examined the cortical representation of vibrotactile detection in humans using event-related fMRI paired with psychophysics. Suprathreshold vibrotactile stimulation activated several areas, including primary (SI) and second somatosensory cortices (SII/PV). For threshold-level stimuli, poststimulus activity in contralateral and ipsilateral SII/PV was the best correlate of detection success. In these areas, evoked signals on hit trials were significantly greater than on missed trials in all participants, and the relative activity level across stimulation amplitudes matched perceptual performance. Activity in the anterior insula and superior temporal gyrus also correlated with hits and misses, suggesting that a "ventral stream" of somatosensory representations may play a crucial role in detection. In contrast, poststimulus activity in Area SI was not well correlated with perception and showed an overall negative response profile for threshold-level stimulation. A different correlate of detection success was, however, observed in SI. Activity in this representation immediately before stimulus onset predicted performance, a finding that was unique to SI. These findings emphasize the potential role of SII/PV in detection, the importance of state dynamics in SI for perception, and the possibility that changes in the temporal and spatial pattern of SI activity may be essential to the optimal representation of threshold-level stimuli for detection.},
	language = {en},
	number = {1},
	urldate = {2020-03-12},
	journal = {Journal of Cognitive Neuroscience},
	author = {Moore, Christopher I. and Crosier, Emilie and Greve, Douglas N. and Savoy, Robert and Merzenich, Michael M. and Dale, Anders M.},
	month = jan,
	year = {2013},
	pages = {49--61}
}

This study examined the cortical representation of vibrotactile detection in humans using event-related fMRI paired with psychophysics. Suprathreshold vibrotactile stimulation activated several areas, including primary (SI) and second somatosensory cortices (SII/PV). For threshold-level stimuli, poststimulus activity in contralateral and ipsilateral SII/PV was the best correlate of detection success. In these areas, evoked signals on hit trials were significantly greater than on missed trials in all participants, and the relative activity level across stimulation amplitudes matched perceptual performance. Activity in the anterior insula and superior temporal gyrus also correlated with hits and misses, suggesting that a "ventral stream" of somatosensory representations may play a crucial role in detection. In contrast, poststimulus activity in Area SI was not well correlated with perception and showed an overall negative response profile for threshold-level stimulation. A different correlate of detection success was, however, observed in SI. Activity in this representation immediately before stimulus onset predicted performance, a finding that was unique to SI. These findings emphasize the potential role of SII/PV in detection, the importance of state dynamics in SI for perception, and the possibility that changes in the temporal and spatial pattern of SI activity may be essential to the optimal representation of threshold-level stimuli for detection.

@article{kerr_mindfulness_2013,
	title = {Mindfulness starts with the body: somatosensory attention and top-down modulation of cortical alpha rhythms in mindfulness meditation},
	volume = {7},
	issn = {1662-5161},
	shorttitle = {Mindfulness starts with the body},
	url = {http://journal.frontiersin.org/article/10.3389/fnhum.2013.00012/abstract},
	doi = {10.3389/fnhum.2013.00012},
	abstract = {Using a common set of mindfulness exercises, mindfulness based stress reduction (MBSR) and mindfulness based cognitive therapy (MBCT) have been shown to reduce distress in chronic pain and decrease risk of depression relapse. These standardized mindfulness (ST-Mindfulness) practices predominantly require attending to breath and body sensations. Here, we offer a novel view of ST-Mindfulness's somatic focus as a form of training for optimizing attentional modulation of 7-14 Hz alpha rhythms that play a key role in filtering inputs to primary sensory neocortex and organizing the flow of sensory information in the brain. In support of the framework, we describe our previous finding that ST-Mindfulness enhanced attentional regulation of alpha in primary somatosensory cortex (SI). The framework allows us to make several predictions. In chronic pain, we predict somatic attention in ST-Mindfulness "de-biases" alpha in SI, freeing up pain-focused attentional resources. In depression relapse, we predict ST-Mindfulness's somatic attention competes with internally focused rumination, as internally focused cognitive processes (including working memory) rely on alpha filtering of sensory input. Our computational model predicts ST-Mindfulness enhances top-down modulation of alpha by facilitating precise alterations in timing and efficacy of SI thalamocortical inputs. We conclude by considering how the framework aligns with Buddhist teachings that mindfulness starts with "mindfulness of the body." Translating this theory into neurophysiology, we hypothesize that with its somatic focus, mindfulness' top-down alpha rhythm modulation in SI enhances gain control which, in turn, sensitizes practitioners to better detect and regulate when the mind wanders from its somatic focus. This enhanced regulation of somatic mind-wandering may be an important early stage of mindfulness training that leads to enhanced cognitive regulation and metacognition.},
	urldate = {2020-03-12},
	journal = {Frontiers in Human Neuroscience},
	author = {Kerr, Catherine E. and Sacchet, Matthew D. and Lazar, Sara W. and Moore, Christopher I. and Jones, Stephanie R.},
	year = {2013},
	file = {Full Text:/Users/jjallen/Zotero/storage/WYLZU6S6/Kerr et al. - 2013 - Mindfulness starts with the body somatosensory at.pdf:application/pdf}
}

Using a common set of mindfulness exercises, mindfulness based stress reduction (MBSR) and mindfulness based cognitive therapy (MBCT) have been shown to reduce distress in chronic pain and decrease risk of depression relapse. These standardized mindfulness (ST-Mindfulness) practices predominantly require attending to breath and body sensations. Here, we offer a novel view of ST-Mindfulness's somatic focus as a form of training for optimizing attentional modulation of 7-14 Hz alpha rhythms that play a key role in filtering inputs to primary sensory neocortex and organizing the flow of sensory information in the brain. In support of the framework, we describe our previous finding that ST-Mindfulness enhanced attentional regulation of alpha in primary somatosensory cortex (SI). The framework allows us to make several predictions. In chronic pain, we predict somatic attention in ST-Mindfulness "de-biases" alpha in SI, freeing up pain-focused attentional resources. In depression relapse, we predict ST-Mindfulness's somatic attention competes with internally focused rumination, as internally focused cognitive processes (including working memory) rely on alpha filtering of sensory input. Our computational model predicts ST-Mindfulness enhances top-down modulation of alpha by facilitating precise alterations in timing and efficacy of SI thalamocortical inputs. We conclude by considering how the framework aligns with Buddhist teachings that mindfulness starts with "mindfulness of the body." Translating this theory into neurophysiology, we hypothesize that with its somatic focus, mindfulness' top-down alpha rhythm modulation in SI enhances gain control which, in turn, sensitizes practitioners to better detect and regulate when the mind wanders from its somatic focus. This enhanced regulation of somatic mind-wandering may be an important early stage of mindfulness training that leads to enhanced cognitive regulation and metacognition.

@article{kahn_optogenetic_2013,
	title = {Optogenetic drive of neocortical pyramidal neurons generates {fMRI} signals that are correlated with spiking activity},
	volume = {1511},
	issn = {00068993},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0006899313003922},
	doi = {10.1016/j.brainres.2013.03.011},
	abstract = {Local fluctuations in the blood oxygenation level-dependent (BOLD) signal serve as the basis of functional magnetic resonance imaging (fMRI). Understanding the correlation between distinct aspects of neural activity and the BOLD response is fundamental to the interpretation of this widely used mapping signal. Analysis of this question requires the ability to precisely manipulate the activity of defined neurons. To achieve such control, we combined optogenetic drive of neocortical neurons with high-resolution (9.4 T) rodent fMRI and detailed analysis of neurophysiological data. Light-driven activation of pyramidal neurons resulted in a positive BOLD response at the stimulated site. To help differentiate the neurophysiological correlate(s) of the BOLD response, we employed light trains of the same average frequency, but with periodic and Poisson distributed pulse times. These different types of pulse trains generated dissociable patterns of single-unit, multi-unit and local field potential (LFP) activity, and of BOLD signals. The BOLD activity exhibited the strongest correlation to spiking activity with increasing rates of stimulation, and, to a first approximation, was linear with pulse delivery rate, while LFP activity showed a weaker correlation. These data provide an example of a strong correlation between spike rate and the BOLD response. This article is part of a Special Issue entitled Optogenetics (7th BRES).},
	language = {en},
	urldate = {2020-03-12},
	journal = {Brain Research},
	author = {Kahn, I. and Knoblich, U. and Desai, M. and Bernstein, J. and Graybiel, A.M. and Boyden, E.S. and Buckner, R.L. and Moore, C.I.},
	month = may,
	year = {2013},
	pages = {33--45},
	file = {Full Text:/Users/jjallen/Zotero/storage/NEE82UMS/Kahn et al. - 2013 - Optogenetic drive of neocortical pyramidal neurons.pdf:application/pdf}
}

Local fluctuations in the blood oxygenation level-dependent (BOLD) signal serve as the basis of functional magnetic resonance imaging (fMRI). Understanding the correlation between distinct aspects of neural activity and the BOLD response is fundamental to the interpretation of this widely used mapping signal. Analysis of this question requires the ability to precisely manipulate the activity of defined neurons. To achieve such control, we combined optogenetic drive of neocortical neurons with high-resolution (9.4 T) rodent fMRI and detailed analysis of neurophysiological data. Light-driven activation of pyramidal neurons resulted in a positive BOLD response at the stimulated site. To help differentiate the neurophysiological correlate(s) of the BOLD response, we employed light trains of the same average frequency, but with periodic and Poisson distributed pulse times. These different types of pulse trains generated dissociable patterns of single-unit, multi-unit and local field potential (LFP) activity, and of BOLD signals. The BOLD activity exhibited the strongest correlation to spiking activity with increasing rates of stimulation, and, to a first approximation, was linear with pulse delivery rate, while LFP activity showed a weaker correlation. These data provide an example of a strong correlation between spike rate and the BOLD response. This article is part of a Special Issue entitled Optogenetics (7th BRES).

@article{schaechter_increase_2012,
	title = {Increase in {Sensorimotor} {Cortex} {Response} to {Somatosensory} {Stimulation} {Over} {Subacute} {Poststroke} {Period} {Correlates} {With} {Motor} {Recovery} in {Hemiparetic} {Patients}},
	volume = {26},
	issn = {1545-9683, 1552-6844},
	url = {http://journals.sagepub.com/doi/10.1177/1545968311421613},
	doi = {10.1177/1545968311421613},
	abstract = {BACKGROUND:

. Somatosensory input to the motor cortex may play a critical role in motor relearning after hemiparetic stroke.
OBJECTIVE:

. The authors tested the hypothesis that motor recovery after hemiparetic stroke relates to changes in responsiveness of the sensorimotor cortex (SMC) to somatosensory input.
METHODS:

. A total of 10 hemiparetic stroke patients underwent serial functional magnetic resonance imaging (fMRI) during tactile stimulation and testing of sensorimotor function over 1 year-at early subacute, late subacute, and chronic poststroke time points.
RESULTS:

. Over the subacute poststroke period, increased responsiveness of the ipsilesional SMC to tactile stimulation of a stroke-affected digit correlated strongly with concurrent gains in motor function. Increased responsiveness of the ipsilesional and contralesional SMC over the subacute period also correlated strongly with motor recovery experienced over the first year poststroke.
CONCLUSIONS:

. These findings suggest that increased responsiveness of the SMC to somatosensory stimulation over the subacute poststroke period may contribute to motor recovery.},
	language = {en},
	number = {4},
	urldate = {2020-03-12},
	journal = {Neurorehabilitation and Neural Repair},
	author = {Schaechter, Judith D. and van Oers, Casper A. M. M. and Groisser, Benjamin N. and Salles, Sara S. and Vangel, Mark G. and Moore, Christopher I. and Dijkhuizen, Rick M.},
	month = may,
	year = {2012},
	pages = {325--334}
}

BACKGROUND: . Somatosensory input to the motor cortex may play a critical role in motor relearning after hemiparetic stroke. OBJECTIVE: . The authors tested the hypothesis that motor recovery after hemiparetic stroke relates to changes in responsiveness of the sensorimotor cortex (SMC) to somatosensory input. METHODS: . A total of 10 hemiparetic stroke patients underwent serial functional magnetic resonance imaging (fMRI) during tactile stimulation and testing of sensorimotor function over 1 year-at early subacute, late subacute, and chronic poststroke time points. RESULTS: . Over the subacute poststroke period, increased responsiveness of the ipsilesional SMC to tactile stimulation of a stroke-affected digit correlated strongly with concurrent gains in motor function. Increased responsiveness of the ipsilesional and contralesional SMC over the subacute period also correlated strongly with motor recovery experienced over the first year poststroke. CONCLUSIONS: . These findings suggest that increased responsiveness of the SMC to somatosensory stimulation over the subacute poststroke period may contribute to motor recovery.

@article{carlen_critical_2012,
	title = {A critical role for {NMDA} receptors in parvalbumin interneurons for gamma rhythm induction and behavior},
	volume = {17},
	issn = {1359-4184, 1476-5578},
	url = {http://www.nature.com/articles/mp201131},
	doi = {10.1038/mp.2011.31},
	abstract = {Synchronous recruitment of fast-spiking (FS) parvalbumin (PV) interneurons generates gamma oscillations, rhythms that emerge during performance of cognitive tasks. Administration of N-methyl-D-aspartate (NMDA) receptor antagonists alters gamma rhythms, and can induce cognitive as well as psychosis-like symptoms in humans. The disruption of NMDA receptor (NMDAR) signaling specifically in FS PV interneurons is therefore hypothesized to give rise to neural network dysfunction that could underlie these symptoms. To address the connection between NMDAR activity, FS PV interneurons, gamma oscillations and behavior, we generated mice lacking NMDAR neurotransmission only in PV cells (PV-Cre/NR1f/f mice). Here, we show that mutant mice exhibit enhanced baseline cortical gamma rhythms, impaired gamma rhythm induction after optogenetic drive of PV interneurons and reduced sensitivity to the effects of NMDAR antagonists on gamma oscillations and stereotypies. Mutant mice show largely normal behaviors except for selective cognitive impairments, including deficits in habituation, working memory and associative learning. Our results provide evidence for the critical role of NMDAR in PV interneurons for expression of normal gamma rhythms and specific cognitive behaviors.},
	language = {en},
	number = {5},
	urldate = {2020-03-12},
	journal = {Molecular Psychiatry},
	author = {Carlén, M and Meletis, K and Siegle, J H and Cardin, J A and Futai, K and Vierling-Claassen, D and Rühlmann, C and Jones, S R and Deisseroth, K and Sheng, M and Moore, C I and Tsai, L-H},
	month = may,
	year = {2012},
	pages = {537--548},
	file = {Full Text:/Users/jjallen/Zotero/storage/54G2GB4A/Carlén et al. - 2012 - A critical role for NMDA receptors in parvalbumin .pdf:application/pdf}
}

Synchronous recruitment of fast-spiking (FS) parvalbumin (PV) interneurons generates gamma oscillations, rhythms that emerge during performance of cognitive tasks. Administration of N-methyl-D-aspartate (NMDA) receptor antagonists alters gamma rhythms, and can induce cognitive as well as psychosis-like symptoms in humans. The disruption of NMDA receptor (NMDAR) signaling specifically in FS PV interneurons is therefore hypothesized to give rise to neural network dysfunction that could underlie these symptoms. To address the connection between NMDAR activity, FS PV interneurons, gamma oscillations and behavior, we generated mice lacking NMDAR neurotransmission only in PV cells (PV-Cre/NR1f/f mice). Here, we show that mutant mice exhibit enhanced baseline cortical gamma rhythms, impaired gamma rhythm induction after optogenetic drive of PV interneurons and reduced sensitivity to the effects of NMDAR antagonists on gamma oscillations and stereotypies. Mutant mice show largely normal behaviors except for selective cognitive impairments, including deficits in habituation, working memory and associative learning. Our results provide evidence for the critical role of NMDAR in PV interneurons for expression of normal gamma rhythms and specific cognitive behaviors.

@article{andermann_brain_2012,
	title = {Brain state-triggered stimulus delivery: {An} efficient tool for probing ongoing brain activity},
	volume = {2},
	issn = {2075-9088},
	shorttitle = {Brain state-triggered stimulus delivery},
	abstract = {What is the relationship between variability in ongoing brain activity preceding a sensory stimulus and subsequent perception of that stimulus? A challenge in the study of this key topic in systems neuroscience is the relative rarity of certain brain 'states'-left to chance, they may seldom align with sensory presentation. We developed a novel method for studying the influence of targeted brain states on subsequent perceptual performance by online identification of spatiotemporal brain activity patterns of interest, and brain-state triggered presentation of subsequent stimuli. This general method was applied to an electroencephalography study of human auditory selective listening. We obtained online, time-varying estimates of the instantaneous direction of neural bias (towards processing left or right ear sounds). Detection of target sounds was influenced by pre-target fluctuations in neural bias, within and across trials. We propose that brain state-triggered stimulus delivery will enable efficient, statistically tractable studies of rare patterns of ongoing activity in single neurons and distributed neural circuits, and their influence on subsequent behavioral and neural responses.},
	language = {eng},
	journal = {Open Journal of Neuroscience},
	author = {Andermann, M. L. and Kauramäki, J. and Palomäki, T. and Moore, C. I. and Hari, R. and Jääskeläinen, I. P. and Sams, M.},
	month = sep,
	year = {2012},
	pmid = {23275858},
	pmcid = {PMC3531547},
	keywords = {auditory, brain-computer interface, online, prestimulus, spontaneous activity}
}

What is the relationship between variability in ongoing brain activity preceding a sensory stimulus and subsequent perception of that stimulus? A challenge in the study of this key topic in systems neuroscience is the relative rarity of certain brain 'states'-left to chance, they may seldom align with sensory presentation. We developed a novel method for studying the influence of targeted brain states on subsequent perceptual performance by online identification of spatiotemporal brain activity patterns of interest, and brain-state triggered presentation of subsequent stimuli. This general method was applied to an electroencephalography study of human auditory selective listening. We obtained online, time-varying estimates of the instantaneous direction of neural bias (towards processing left or right ear sounds). Detection of target sounds was influenced by pre-target fluctuations in neural bias, within and across trials. We propose that brain state-triggered stimulus delivery will enable efficient, statistically tractable studies of rare patterns of ongoing activity in single neurons and distributed neural circuits, and their influence on subsequent behavioral and neural responses.

@article{siegle_cortical_2011,
	title = {Cortical {Circuits}: {Finding} {Balance} in the {Brain}},
	volume = {21},
	issn = {09609822},
	shorttitle = {Cortical {Circuits}},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0960982211011870},
	doi = {10.1016/j.cub.2011.10.026},
	abstract = {Maintaining the right balance between excitation and inhibition is crucial to healthy brain function. A recent study has used optogenetics to show how quickly and effectively inhibition clamps down a novel burst of excitation in the neocortex.},
	language = {en},
	number = {23},
	urldate = {2020-03-12},
	journal = {Current Biology},
	author = {Siegle, Joshua H. and Moore, Christopher I.},
	month = dec,
	year = {2011},
	pages = {R956--R957},
	file = {Full Text:/Users/jjallen/Zotero/storage/FQPLFKMP/Siegle and Moore - 2011 - Cortical Circuits Finding Balance in the Brain.pdf:application/pdf}
}

Maintaining the right balance between excitation and inhibition is crucial to healthy brain function. A recent study has used optogenetics to show how quickly and effectively inhibition clamps down a novel burst of excitation in the neocortex.

@inproceedings{siegle_chronically_2011,
	address = {Boston, MA},
	title = {Chronically implanted hyperdrive for cortical recording and optogenetic control in behaving mice},
	isbn = {978-1-4577-1589-1 978-1-4244-4121-1 978-1-4244-4122-8},
	url = {http://ieeexplore.ieee.org/document/6091856/},
	doi = {10.1109/IEMBS.2011.6091856},
	abstract = {Neural stimulation technology has undergone a revolutionary advance with the introduction of light sensitive ion channels and pumps into genetically identified subsets of cells. To exploit this technology, it is necessary to incorporate optical elements into traditional electrophysiology devices. Here we describe the design, construction and use of a "hyperdrive" capable of simultaneous electrical recordings and optical stimulation. The device consists of multiple microdrives for moving electrodes independently and a stationary fiber for delivering light to the tissue surrounding the electrodes. We present data demonstrating the effectiveness of inhibitory recruitment via optical stimulation and its interaction with physiological and behavioral states, determined by electrophysiological recording and videographic monitoring.},
	urldate = {2020-03-12},
	booktitle = {2011 {Annual} {International} {Conference} of the {IEEE} {Engineering} in {Medicine} and {Biology} {Society}},
	publisher = {IEEE},
	author = {Siegle, J. H. and Carlen, M. and Meletis, K. and {Li-Huei Tsai} and Moore, C. I. and Ritt, J.},
	month = aug,
	year = {2011},
	pages = {7529--7532}
}

Neural stimulation technology has undergone a revolutionary advance with the introduction of light sensitive ion channels and pumps into genetically identified subsets of cells. To exploit this technology, it is necessary to incorporate optical elements into traditional electrophysiology devices. Here we describe the design, construction and use of a "hyperdrive" capable of simultaneous electrical recordings and optical stimulation. The device consists of multiple microdrives for moving electrodes independently and a stationary fiber for delivering light to the tissue surrounding the electrodes. We present data demonstrating the effectiveness of inhibitory recruitment via optical stimulation and its interaction with physiological and behavioral states, determined by electrophysiological recording and videographic monitoring.

@article{kerr_effects_2011,
	title = {Effects of mindfulness meditation training on anticipatory alpha modulation in primary somatosensory cortex},
	volume = {85},
	issn = {03619230},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0361923011001341},
	doi = {10.1016/j.brainresbull.2011.03.026},
	abstract = {During selective attention, ∼7-14 Hz alpha rhythms are modulated in early sensory cortices, suggesting a mechanistic role for these dynamics in perception. Here, we investigated whether alpha modulation can be enhanced by "mindfulness" meditation (MM), a program training practitioners in sustained attention to body and breath-related sensations. We hypothesized that participants in the MM group would exhibit enhanced alpha power modulation in a localized representation in the primary somatosensory neocortex in response to a cue, as compared to participants in the control group. Healthy subjects were randomized to 8-weeks of MM training or a control group. Using magnetoencephalographic (MEG) recording of the SI finger representation, we found meditators demonstrated enhanced alpha power modulation in response to a cue. This finding is the first to show enhanced local alpha modulation following sustained attentional training, and implicates this form of enhanced dynamic neural regulation in the behavioral effects of meditative practice.},
	language = {en},
	number = {3-4},
	urldate = {2020-03-12},
	journal = {Brain Research Bulletin},
	author = {Kerr, Catherine E. and Jones, Stephanie R. and Wan, Qian and Pritchett, Dominique L. and Wasserman, Rachel H. and Wexler, Anna and Villanueva, Joel J. and Shaw, Jessica R. and Lazar, Sara W. and Kaptchuk, Ted J. and Littenberg, Ronnie and Hämäläinen, Matti S. and Moore, Christopher I.},
	month = may,
	year = {2011},
	pages = {96--103}
}

During selective attention, ∼7-14 Hz alpha rhythms are modulated in early sensory cortices, suggesting a mechanistic role for these dynamics in perception. Here, we investigated whether alpha modulation can be enhanced by "mindfulness" meditation (MM), a program training practitioners in sustained attention to body and breath-related sensations. We hypothesized that participants in the MM group would exhibit enhanced alpha power modulation in a localized representation in the primary somatosensory neocortex in response to a cue, as compared to participants in the control group. Healthy subjects were randomized to 8-weeks of MM training or a control group. Using magnetoencephalographic (MEG) recording of the SI finger representation, we found meditators demonstrated enhanced alpha power modulation in response to a cue. This finding is the first to show enhanced local alpha modulation following sustained attentional training, and implicates this form of enhanced dynamic neural regulation in the behavioral effects of meditative practice.

@article{kahn_characterization_2011,
	title = {Characterization of the {Functional} {MRI} {Response} {Temporal} {Linearity} via {Optical} {Control} of {Neocortical} {Pyramidal} {Neurons}},
	volume = {31},
	issn = {0270-6474, 1529-2401},
	url = {http://www.jneurosci.org/cgi/doi/10.1523/JNEUROSCI.0007-11.2011},
	doi = {10.1523/JNEUROSCI.0007-11.2011},
	abstract = {The blood oxygenation level-dependent (BOLD) signal serves as the basis for human functional MRI (fMRI). Knowledge of the properties of the BOLD signal, such as how linear its response is to sensory stimuli, is essential for the design and interpretation of fMRI experiments. Here, we combined the cell-type and site-specific causal control provided by optogenetics and fMRI (opto-fMRI) in mice to test the linearity of BOLD signals driven by locally induced excitatory activity. We employed high-resolution mouse fMRI at 9.4 tesla to measure the BOLD response, and extracellular electrophysiological recordings to measure the effects of stimulation on single unit, multiunit, and local field potential activity. Optically driven stimulation of layer V neocortical pyramidal neurons resulted in a positive local BOLD response at the stimulated site. Consistent with a linear transform model, this locally driven BOLD response summated in response to closely spaced trains of stimulation. These properties were equivalent to responses generated through the multisynaptic method of driving neocortical activity by tactile sensory stimulation, and paralleled changes in electrophysiological measures. These results illustrate the potential of the opto-fMRI method and reinforce the critical assumption of human functional neuroimaging that--to first approximation--the BOLD response tracks local neural activity levels.},
	language = {en},
	number = {42},
	urldate = {2020-03-12},
	journal = {Journal of Neuroscience},
	author = {Kahn, I. and Desai, M. and Knoblich, U. and Bernstein, J. and Henninger, M. and Graybiel, A. M. and Boyden, E. S. and Buckner, R. L. and Moore, C. I.},
	month = oct,
	year = {2011},
	pages = {15086--15091},
	file = {Full Text:/Users/jjallen/Zotero/storage/ZK9Z3A5I/Kahn et al. - 2011 - Characterization of the Functional MRI Response Te.pdf:application/pdf}
}

The blood oxygenation level-dependent (BOLD) signal serves as the basis for human functional MRI (fMRI). Knowledge of the properties of the BOLD signal, such as how linear its response is to sensory stimuli, is essential for the design and interpretation of fMRI experiments. Here, we combined the cell-type and site-specific causal control provided by optogenetics and fMRI (opto-fMRI) in mice to test the linearity of BOLD signals driven by locally induced excitatory activity. We employed high-resolution mouse fMRI at 9.4 tesla to measure the BOLD response, and extracellular electrophysiological recordings to measure the effects of stimulation on single unit, multiunit, and local field potential activity. Optically driven stimulation of layer V neocortical pyramidal neurons resulted in a positive local BOLD response at the stimulated site. Consistent with a linear transform model, this locally driven BOLD response summated in response to closely spaced trains of stimulation. These properties were equivalent to responses generated through the multisynaptic method of driving neocortical activity by tactile sensory stimulation, and paralleled changes in electrophysiological measures. These results illustrate the potential of the opto-fMRI method and reinforce the critical assumption of human functional neuroimaging that–to first approximation–the BOLD response tracks local neural activity levels.

@article{halassa_selective_2011,
	title = {Selective optical drive of thalamic reticular nucleus generates thalamic bursts and cortical spindles},
	volume = {14},
	issn = {1097-6256, 1546-1726},
	url = {http://www.nature.com/articles/nn.2880},
	doi = {10.1038/nn.2880},
	abstract = {The thalamic reticular nucleus (TRN) is hypothesized to regulate neocortical rhythms and behavioral states. Using optogenetics and multi-electrode recording in behaving mice, we found that brief selective drive of TRN switched the thalamocortical firing mode from tonic to bursting and generated state-dependent neocortical spindles. These findings provide causal support for the involvement of the TRN in state regulation in vivo and introduce a new model for addressing the role of this structure in behavior.},
	language = {en},
	number = {9},
	urldate = {2020-03-12},
	journal = {Nature Neuroscience},
	author = {Halassa, Michael M and Siegle, Joshua H and Ritt, Jason T and Ting, Jonathan T and Feng, Guoping and Moore, Christopher I},
	month = sep,
	year = {2011},
	pages = {1118--1120},
	file = {Accepted Version:/Users/jjallen/Zotero/storage/XVWQJ3W4/Halassa et al. - 2011 - Selective optical drive of thalamic reticular nucl.pdf:application/pdf}
}

The thalamic reticular nucleus (TRN) is hypothesized to regulate neocortical rhythms and behavioral states. Using optogenetics and multi-electrode recording in behaving mice, we found that brief selective drive of TRN switched the thalamocortical firing mode from tonic to bursting and generated state-dependent neocortical spindles. These findings provide causal support for the involvement of the TRN in state regulation in vivo and introduce a new model for addressing the role of this structure in behavior.

@article{desai_mapping_2011,
	title = {Mapping brain networks in awake mice using combined optical neural control and {fMRI}},
	volume = {105},
	issn = {0022-3077, 1522-1598},
	url = {https://www.physiology.org/doi/10.1152/jn.00828.2010},
	doi = {10.1152/jn.00828.2010},
	abstract = {Behaviors and brain disorders involve neural circuits that are widely distributed in the brain. The ability to map the functional connectivity of distributed circuits, and to assess how this connectivity evolves over time, will be facilitated by methods for characterizing the network impact of activating a specific subcircuit, cell type, or projection pathway. We describe here an approach using high-resolution blood oxygenation level-dependent (BOLD) functional MRI (fMRI) of the awake mouse brain-to measure the distributed BOLD response evoked by optical activation of a local, defined cell class expressing the light-gated ion channel channelrhodopsin-2 (ChR2). The utility of this opto-fMRI approach was explored by identifying known cortical and subcortical targets of pyramidal cells of the primary somatosensory cortex (SI) and by analyzing how the set of regions recruited by optogenetically driven SI activity differs between the awake and anesthetized states. Results showed positive BOLD responses in a distributed network that included secondary somatosensory cortex (SII), primary motor cortex (MI), caudoputamen (CP), and contralateral SI (c-SI). Measures in awake compared with anesthetized mice (0.7\% isoflurane) showed significantly increased BOLD response in the local region (SI) and indirectly stimulated regions (SII, MI, CP, and c-SI), as well as increased BOLD signal temporal correlations between pairs of regions. These collective results suggest opto-fMRI can provide a controlled means for characterizing the distributed network downstream of a defined cell class in the awake brain. Opto-fMRI may find use in examining causal links between defined circuit elements in diverse behaviors and pathologies.},
	language = {en},
	number = {3},
	urldate = {2020-03-12},
	journal = {Journal of Neurophysiology},
	author = {Desai, M. and Kahn, I. and Knoblich, U. and Bernstein, J. and Atallah, H. and Yang, A. and Kopell, N. and Buckner, R. L. and Graybiel, A. M. and Moore, C. I. and Boyden, E. S.},
	month = mar,
	year = {2011},
	pages = {1393--1405},
	file = {Submitted Version:/Users/jjallen/Zotero/storage/9XLZXWZ5/Desai et al. - 2011 - Mapping brain networks in awake mice using combine.pdf:application/pdf}
}

Behaviors and brain disorders involve neural circuits that are widely distributed in the brain. The ability to map the functional connectivity of distributed circuits, and to assess how this connectivity evolves over time, will be facilitated by methods for characterizing the network impact of activating a specific subcircuit, cell type, or projection pathway. We describe here an approach using high-resolution blood oxygenation level-dependent (BOLD) functional MRI (fMRI) of the awake mouse brain-to measure the distributed BOLD response evoked by optical activation of a local, defined cell class expressing the light-gated ion channel channelrhodopsin-2 (ChR2). The utility of this opto-fMRI approach was explored by identifying known cortical and subcortical targets of pyramidal cells of the primary somatosensory cortex (SI) and by analyzing how the set of regions recruited by optogenetically driven SI activity differs between the awake and anesthetized states. Results showed positive BOLD responses in a distributed network that included secondary somatosensory cortex (SII), primary motor cortex (MI), caudoputamen (CP), and contralateral SI (c-SI). Measures in awake compared with anesthetized mice (0.7% isoflurane) showed significantly increased BOLD response in the local region (SI) and indirectly stimulated regions (SII, MI, CP, and c-SI), as well as increased BOLD signal temporal correlations between pairs of regions. These collective results suggest opto-fMRI can provide a controlled means for characterizing the distributed network downstream of a defined cell class in the awake brain. Opto-fMRI may find use in examining causal links between defined circuit elements in diverse behaviors and pathologies.

@article{ziegler_transformations_2010,
	title = {Transformations in oscillatory activity and evoked responses in primary somatosensory cortex in middle age: {A} combined computational neural modeling and {MEG} study},
	volume = {52},
	issn = {10538119},
	shorttitle = {Transformations in oscillatory activity and evoked responses in primary somatosensory cortex in middle age},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S1053811910001527},
	doi = {10.1016/j.neuroimage.2010.02.004},
	abstract = {Oscillatory brain rhythms and evoked responses are widely believed to impact cognition, but relatively little is known about how these measures are affected by healthy aging. The present study used MEG to examine age-related changes in spontaneous oscillations and tactile evoked responses in primary somatosensory cortex (SI) in healthy young (YA) and middle-aged (MA) adults. To make specific predictions about neurophysiological changes that mediate age-related MEG changes, we applied a biophysically realistic model of SI that accurately reproduces SI MEG mu rhythms, containing alpha (7-14 Hz) and beta (15-30 Hz) components, and evoked responses. Analyses of MEG data revealed a significant increase in prestimulus mu power in SI, driven predominately by greater mu-beta dominance, and a larger and delayed M70 peak in the SI evoked response in MA. Previous analysis with our computational model showed that the SI mu rhythm could be reproduced with a stochastic sequence of rhythmic approximately 10 Hz feedforward (FF) input to the granular layers of SI (representative of lemniscal thalamic input) followed nearly simultaneously by approximately 10 Hz feedback (FB) input to the supragranular layers (representative of input from high order cortical or non-specific thalamic sources) (Jones et al., 2009). In the present study, the model further predicted that the rhythmic FF and FB inputs become stronger with age. Further, the FB input is predicted to arrive more synchronously to SI on each cycle of the 10 Hz input in MA. The simulated neurophysiological changes are sufficient to account for the age-related differences in both prestimulus mu rhythms and evoked responses. Thus, the model predicts that a single set of neurophysiological changes intimately links these age-related changes in neural dynamics.},
	language = {en},
	number = {3},
	urldate = {2020-03-12},
	journal = {NeuroImage},
	author = {Ziegler, David A. and Pritchett, Dominique L. and Hosseini-Varnamkhasti, Paymon and Corkin, Suzanne and Hämäläinen, Matti and Moore, Christopher I. and Jones, Stephanie R.},
	month = sep,
	year = {2010},
	pages = {897--912},
	file = {Accepted Version:/Users/jjallen/Zotero/storage/X22WQ4BW/Ziegler et al. - 2010 - Transformations in oscillatory activity and evoked.pdf:application/pdf}
}

Oscillatory brain rhythms and evoked responses are widely believed to impact cognition, but relatively little is known about how these measures are affected by healthy aging. The present study used MEG to examine age-related changes in spontaneous oscillations and tactile evoked responses in primary somatosensory cortex (SI) in healthy young (YA) and middle-aged (MA) adults. To make specific predictions about neurophysiological changes that mediate age-related MEG changes, we applied a biophysically realistic model of SI that accurately reproduces SI MEG mu rhythms, containing alpha (7-14 Hz) and beta (15-30 Hz) components, and evoked responses. Analyses of MEG data revealed a significant increase in prestimulus mu power in SI, driven predominately by greater mu-beta dominance, and a larger and delayed M70 peak in the SI evoked response in MA. Previous analysis with our computational model showed that the SI mu rhythm could be reproduced with a stochastic sequence of rhythmic approximately 10 Hz feedforward (FF) input to the granular layers of SI (representative of lemniscal thalamic input) followed nearly simultaneously by approximately 10 Hz feedback (FB) input to the supragranular layers (representative of input from high order cortical or non-specific thalamic sources) (Jones et al., 2009). In the present study, the model further predicted that the rhythmic FF and FB inputs become stronger with age. Further, the FB input is predicted to arrive more synchronously to SI on each cycle of the 10 Hz input in MA. The simulated neurophysiological changes are sufficient to account for the age-related differences in both prestimulus mu rhythms and evoked responses. Thus, the model predicts that a single set of neurophysiological changes intimately links these age-related changes in neural dynamics.

@article{vijayan_activity_2010,
	title = {Activity in the {Barrel} {Cortex} {During} {Active} {Behavior} and {Sleep}},
	volume = {103},
	issn = {0022-3077, 1522-1598},
	url = {https://www.physiology.org/doi/10.1152/jn.00474.2009},
	doi = {10.1152/jn.00474.2009},
	abstract = {The rate at which neurons fire has wide-reaching implications for the coding schemes used by neural systems. Despite the extensive use of the barrel cortex as a model system, relatively few studies have examined the rate of sensory activity in single neurons in freely moving animals. We examined the activity of barrel cortex neurons in behaving animals during sensory cue interaction, during non–stimulus-related activity, during various states of sleep, and during the administration of isoflurane. The activity of regular-spiking units (RSUs: predominantly excitatory neurons) and fast spiking units (FSUs: a subtype of inhibitory interneurons) was examined separately. We characterized activity by calculating neural firing rates, because several reports have emphasized the low firing rates in this system, reporting that both baseline activity and stimulus evoked activity is {\textless}1 Hz. We report that, during sensory cue interaction or non–stimulus-related activity, the majority of RSUs in rat barrel cortex fired at rates significantly {\textgreater}1 Hz, with 27.4\% showing rates above 10 Hz during cue interaction. Even during slow wave sleep, which had the lowest mean and median firing rates of any nonanesthetized state observed, 80.0\% of RSUs fired above 1 Hz. During all of the nonanesthetized states observed 100\% of the FSUs fired well above 1 Hz. When rats were administered isoflurane and at a depth of anesthesia used in standard in vivo electrophysiological preparations, all of the RSUs fired below 1 Hz. We also found that {\textgreater}80\% of RSUs either upmodulated or downmodulated their firing during cue interaction. These data suggest that low firing rates do not typify the output of the barrel cortex during awake activity and during sleep and indicate that sensory coding at both the individual and population levels may be nonsparse.},
	language = {en},
	number = {4},
	urldate = {2020-03-12},
	journal = {Journal of Neurophysiology},
	author = {Vijayan, Sujith and Hale, Greg J. and Moore, Christopher I. and Brown, Emery N. and Wilson, Matthew},
	month = apr,
	year = {2010},
	pages = {2074--2084},
	file = {Submitted Version:/Users/jjallen/Zotero/storage/KLWA5QR9/Vijayan et al. - 2010 - Activity in the Barrel Cortex During Active Behavi.pdf:application/pdf}
}

The rate at which neurons fire has wide-reaching implications for the coding schemes used by neural systems. Despite the extensive use of the barrel cortex as a model system, relatively few studies have examined the rate of sensory activity in single neurons in freely moving animals. We examined the activity of barrel cortex neurons in behaving animals during sensory cue interaction, during non–stimulus-related activity, during various states of sleep, and during the administration of isoflurane. The activity of regular-spiking units (RSUs: predominantly excitatory neurons) and fast spiking units (FSUs: a subtype of inhibitory interneurons) was examined separately. We characterized activity by calculating neural firing rates, because several reports have emphasized the low firing rates in this system, reporting that both baseline activity and stimulus evoked activity is \textless1 Hz. We report that, during sensory cue interaction or non–stimulus-related activity, the majority of RSUs in rat barrel cortex fired at rates significantly \textgreater1 Hz, with 27.4% showing rates above 10 Hz during cue interaction. Even during slow wave sleep, which had the lowest mean and median firing rates of any nonanesthetized state observed, 80.0% of RSUs fired above 1 Hz. During all of the nonanesthetized states observed 100% of the FSUs fired well above 1 Hz. When rats were administered isoflurane and at a depth of anesthesia used in standard in vivo electrophysiological preparations, all of the RSUs fired below 1 Hz. We also found that \textgreater80% of RSUs either upmodulated or downmodulated their firing during cue interaction. These data suggest that low firing rates do not typify the output of the barrel cortex during awake activity and during sleep and indicate that sensory coding at both the individual and population levels may be nonsparse.

@article{vierling-claassen_computational_2010,
	title = {Computational {Modeling} of {Distinct} {Neocortical} {Oscillations} {Driven} by {Cell}-{Type} {Selective} {Optogenetic} {Drive}: {Separable} {Resonant} {Circuits} {Controlled} by {Low}-{Threshold} {Spiking} and {Fast}-{Spiking} {Interneurons}},
	volume = {4},
	issn = {1662-5161},
	shorttitle = {Computational {Modeling} of {Distinct} {Neocortical} {Oscillations} {Driven} by {Cell}-{Type} {Selective} {Optogenetic} {Drive}},
	url = {http://journal.frontiersin.org/article/10.3389/fnhum.2010.00198/abstract},
	doi = {10.3389/fnhum.2010.00198},
	abstract = {Selective optogenetic drive of fast-spiking (FS) interneurons (INs) leads to enhanced local field potential (LFP) power across the traditional "gamma" frequency band (20-80 Hz; Cardin et al., 2009). In contrast, drive to regular-spiking (RS) pyramidal cells enhances power at lower frequencies, with a peak at 8 Hz. The first result is consistent with previous computational studies emphasizing the role of FS and the time constant of GABA(A) synaptic inhibition in gamma rhythmicity. However, the same theoretical models do not typically predict low-frequency LFP enhancement with RS drive. To develop hypotheses as to how the same network can support these contrasting behaviors, we constructed a biophysically principled network model of primary somatosensory neocortex containing FS, RS, and low-threshold spiking (LTS) INs. Cells were modeled with detailed cell anatomy and physiology, multiple dendritic compartments, and included active somatic and dendritic ionic currents. Consistent with prior studies, the model demonstrated gamma resonance during FS drive, dependent on the time constant of GABA(A) inhibition induced by synchronous FS activity. Lower-frequency enhancement during RS drive was replicated only on inclusion of an inhibitory LTS population, whose activation was critically dependent on RS synchrony and evoked longer-lasting inhibition. Our results predict that differential recruitment of FS and LTS inhibitory populations is essential to the observed cortical dynamics and may provide a means for amplifying the natural expression of distinct oscillations in normal cortical processing.},
	urldate = {2020-03-12},
	journal = {Frontiers in Human Neuroscience},
	author = {Vierling-Claassen, Dorea and Cardin, Jessica A. and Moore, Christopher I. and Jones, Stephanie R.},
	year = {2010},
	file = {Full Text:/Users/jjallen/Zotero/storage/3E2E7FAT/Vierling-Claassen et al. - 2010 - Computational Modeling of Distinct Neocortical Osc.pdf:application/pdf}
}

Selective optogenetic drive of fast-spiking (FS) interneurons (INs) leads to enhanced local field potential (LFP) power across the traditional "gamma" frequency band (20-80 Hz; Cardin et al., 2009). In contrast, drive to regular-spiking (RS) pyramidal cells enhances power at lower frequencies, with a peak at 8 Hz. The first result is consistent with previous computational studies emphasizing the role of FS and the time constant of GABA(A) synaptic inhibition in gamma rhythmicity. However, the same theoretical models do not typically predict low-frequency LFP enhancement with RS drive. To develop hypotheses as to how the same network can support these contrasting behaviors, we constructed a biophysically principled network model of primary somatosensory neocortex containing FS, RS, and low-threshold spiking (LTS) INs. Cells were modeled with detailed cell anatomy and physiology, multiple dendritic compartments, and included active somatic and dendritic ionic currents. Consistent with prior studies, the model demonstrated gamma resonance during FS drive, dependent on the time constant of GABA(A) inhibition induced by synchronous FS activity. Lower-frequency enhancement during RS drive was replicated only on inclusion of an inhibitory LTS population, whose activation was critically dependent on RS synchrony and evoked longer-lasting inhibition. Our results predict that differential recruitment of FS and LTS inhibitory populations is essential to the observed cortical dynamics and may provide a means for amplifying the natural expression of distinct oscillations in normal cortical processing.

@article{moore_neocortical_2010,
	title = {Neocortical {Interneurons}: {From} {Diversity}, {Strength}},
	volume = {142},
	issn = {00928674},
	shorttitle = {Neocortical {Interneurons}},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0092867410007749},
	doi = {10.1016/j.cell.2010.07.005},
	abstract = {Interneurons in the neocortex of the brain are small, locally projecting inhibitory GABAergic cells with a broad array of anatomical and physiological properties. The diversity of interneurons is believed to be crucial for regulating myriad operations in the neocortex. Here, we describe current theories about how interneuron diversity may support distinct neocortical processes that underlie perception.},
	language = {en},
	number = {2},
	urldate = {2020-03-12},
	journal = {Cell},
	author = {Moore, Christopher I. and Carlen, Marie and Knoblich, Ulf and Cardin, Jessica A.},
	month = jul,
	year = {2010},
	pages = {184--188},
	file = {Full Text:/Users/jjallen/Zotero/storage/QGYE4CW2/Moore et al. - 2010 - Neocortical Interneurons From Diversity, Strength.pdf:application/pdf}
}

Interneurons in the neocortex of the brain are small, locally projecting inhibitory GABAergic cells with a broad array of anatomical and physiological properties. The diversity of interneurons is believed to be crucial for regulating myriad operations in the neocortex. Here, we describe current theories about how interneuron diversity may support distinct neocortical processes that underlie perception.

@article{knoblich_what_2010,
	title = {What do {We} {Gain} from {Gamma}? {Local} {Dynamic} {Gain} {Modulation} {Drives} {Enhanced} {Efficacy} and {Efficiency} of {Signal} {Transmission}},
	volume = {04},
	issn = {1662-5161},
	shorttitle = {What do {We} {Gain} from {Gamma}?},
	url = {http://journal.frontiersin.org/article/10.3389/fnhum.2010.00185/abstract},
	doi = {10.3389/fnhum.2010.00185},
	abstract = {Gamma oscillations in neocortex are hypothesized to improve information transmission between groups of neurons. We recently showed that optogenetic drive of fast-spiking interneurons (FS) at 40 Hz in mouse neocortex in vivo modulates the spike count and precision of sensory evoked responses. At specific phases of alignment between stimuli and FS activation, total evoked spike count was unchanged compared to baseline, but precision was increased. In the present study, we used computational modeling to investigate the origin of these local transformations, and to make predictions about their impact on downstream signal transmission. We replicated the prior experimental findings, and found that the local gain observed can be explained by mutual inhibition of fast-spiking interneurons, leading to more robust sensory-driven spiking in a brief temporal window post-stimulus, increasing local synchrony. Enhanced spiking in a second neocortical area, without a net increase in overall driven spikes in the first area, resulted from faster depolarization of target neurons due to increased pre-synaptic synchrony. In addition, we found that the precise temporal structure of spiking in the first area impacted the gain between cortical areas. The optimal spike distribution matched the "window of opportunity" defined by the timing of inhibition in the target area: spiking beyond this window did not contribute to downstream spike generation, leading to decreased overall gain. This result predicts that efficient transmission between neocortical areas requires a mechanism to dynamically match the temporal structure of the output of one area to the timing of inhibition in the recipient zone.},
	urldate = {2020-03-12},
	journal = {Frontiers in Human Neuroscience},
	author = {Knoblich, Ulf and Siegle, Joshua H. and Pritchett, Dominique L. and Moore, Christopher I.},
	year = {2010},
	file = {Full Text:/Users/jjallen/Zotero/storage/I3XRN6XE/Knoblich et al. - 2010 - What do We Gain from Gamma Local Dynamic Gain Mod.pdf:application/pdf}
}

Gamma oscillations in neocortex are hypothesized to improve information transmission between groups of neurons. We recently showed that optogenetic drive of fast-spiking interneurons (FS) at 40 Hz in mouse neocortex in vivo modulates the spike count and precision of sensory evoked responses. At specific phases of alignment between stimuli and FS activation, total evoked spike count was unchanged compared to baseline, but precision was increased. In the present study, we used computational modeling to investigate the origin of these local transformations, and to make predictions about their impact on downstream signal transmission. We replicated the prior experimental findings, and found that the local gain observed can be explained by mutual inhibition of fast-spiking interneurons, leading to more robust sensory-driven spiking in a brief temporal window post-stimulus, increasing local synchrony. Enhanced spiking in a second neocortical area, without a net increase in overall driven spikes in the first area, resulted from faster depolarization of target neurons due to increased pre-synaptic synchrony. In addition, we found that the precise temporal structure of spiking in the first area impacted the gain between cortical areas. The optimal spike distribution matched the "window of opportunity" defined by the timing of inhibition in the target area: spiking beyond this window did not contribute to downstream spike generation, leading to decreased overall gain. This result predicts that efficient transmission between neocortical areas requires a mechanism to dynamically match the temporal structure of the output of one area to the timing of inhibition in the recipient zone.

@article{jones_cued_2010,
	title = {Cued {Spatial} {Attention} {Drives} {Functionally} {Relevant} {Modulation} of the {Mu} {Rhythm} in {Primary} {Somatosensory} {Cortex}},
	volume = {30},
	issn = {0270-6474, 1529-2401},
	url = {http://www.jneurosci.org/cgi/doi/10.1523/JNEUROSCI.2969-10.2010},
	doi = {10.1523/JNEUROSCI.2969-10.2010},
	abstract = {Cued spatial attention modulates functionally relevant alpha rhythms in visual cortices in humans. Here, we present evidence for analogous phenomena in primary somatosensory neocortex (SI). Using magnetoencephalography, we measured changes in the SI mu rhythm containing mu-alpha (7-14 Hz) and mu-beta (15-29 Hz) components. We found that cued attention impacted mu-alpha in the somatopically localized hand representation in SI, showing decreased power after attention was cued to the hand and increased power after attention was cued to the foot, with significant differences observed 500-1100 ms after cue. Mu-beta showed differences in a time window 800-850 ms after cue. The visual cue also drove an early evoked response beginning ∼70 ms after cue with distinct peaks modulated with cued attention. Distinct components of the tactile stimulus-evoked response were also modulated with cued attention. Analysis of a second dataset showed that, on a trial-by-trial basis, tactile detection probabilities decreased linearly with prestimulus mu-alpha and mu-beta power. These results support the growing consensus that cue-induced alpha modulation is a functionally relevant sensory gating mechanism deployed by attention. Further, while cued attention had a weaker effect on the allocation of mu-beta, oscillations in this band also predicted tactile detection.},
	language = {en},
	number = {41},
	urldate = {2020-03-12},
	journal = {Journal of Neuroscience},
	author = {Jones, S. R. and Kerr, C. E. and Wan, Q. and Pritchett, D. L. and Hamalainen, M. and Moore, C. I.},
	month = oct,
	year = {2010},
	pages = {13760--13765},
	file = {Full Text:/Users/jjallen/Zotero/storage/7ARPQ6XJ/Jones et al. - 2010 - Cued Spatial Attention Drives Functionally Relevan.pdf:application/pdf}
}

Cued spatial attention modulates functionally relevant alpha rhythms in visual cortices in humans. Here, we present evidence for analogous phenomena in primary somatosensory neocortex (SI). Using magnetoencephalography, we measured changes in the SI mu rhythm containing mu-alpha (7-14 Hz) and mu-beta (15-29 Hz) components. We found that cued attention impacted mu-alpha in the somatopically localized hand representation in SI, showing decreased power after attention was cued to the hand and increased power after attention was cued to the foot, with significant differences observed 500-1100 ms after cue. Mu-beta showed differences in a time window 800-850 ms after cue. The visual cue also drove an early evoked response beginning ∼70 ms after cue with distinct peaks modulated with cued attention. Distinct components of the tactile stimulus-evoked response were also modulated with cued attention. Analysis of a second dataset showed that, on a trial-by-trial basis, tactile detection probabilities decreased linearly with prestimulus mu-alpha and mu-beta power. These results support the growing consensus that cue-induced alpha modulation is a functionally relevant sensory gating mechanism deployed by attention. Further, while cued attention had a weaker effect on the allocation of mu-beta, oscillations in this band also predicted tactile detection.

@article{cardin_targeted_2010,
	title = {Targeted optogenetic stimulation and recording of neurons in vivo using cell-type-specific expression of {Channelrhodopsin}-2},
	volume = {5},
	issn = {1754-2189, 1750-2799},
	url = {http://www.nature.com/articles/nprot.2009.228},
	doi = {10.1038/nprot.2009.228},
	abstract = {A major long-term goal of systems neuroscience is to identify the different roles of neural subtypes in brain circuit function. The ability to causally manipulate selective cell types is critical to meeting this goal. This protocol describes techniques for optically stimulating specific populations of excitatory neurons and inhibitory interneurons in vivo in combination with electrophysiology. Cell type selectivity is obtained using Cre-dependent expression of the light-activated channel Channelrhodopsin-2. We also describe approaches for minimizing optical interference with simultaneous extracellular and intracellular recording. These optogenetic techniques provide a spatially and temporally precise means of studying neural activity in the intact brain and allow a detailed examination of the effect of evoked activity on the surrounding local neural network. Injection of viral vectors requires 30-45 min, and in vivo electrophysiology with optogenetic stimulation requires 1-4 h.},
	language = {en},
	number = {2},
	urldate = {2020-03-12},
	journal = {Nature Protocols},
	author = {Cardin, Jessica A and Carlén, Marie and Meletis, Konstantinos and Knoblich, Ulf and Zhang, Feng and Deisseroth, Karl and Tsai, Li-Huei and Moore, Christopher I},
	month = feb,
	year = {2010},
	pages = {247--254},
	file = {Full Text:/Users/jjallen/Zotero/storage/N3EGLYNX/Cardin et al. - 2010 - Targeted optogenetic stimulation and recording of .pdf:application/pdf}
}

A major long-term goal of systems neuroscience is to identify the different roles of neural subtypes in brain circuit function. The ability to causally manipulate selective cell types is critical to meeting this goal. This protocol describes techniques for optically stimulating specific populations of excitatory neurons and inhibitory interneurons in vivo in combination with electrophysiology. Cell type selectivity is obtained using Cre-dependent expression of the light-activated channel Channelrhodopsin-2. We also describe approaches for minimizing optical interference with simultaneous extracellular and intracellular recording. These optogenetic techniques provide a spatially and temporally precise means of studying neural activity in the intact brain and allow a detailed examination of the effect of evoked activity on the surrounding local neural network. Injection of viral vectors requires 30-45 min, and in vivo electrophysiology with optogenetic stimulation requires 1-4 h.

@article{konkle_motion_2009,
	title = {Motion {Aftereffects} {Transfer} between {Touch} and {Vision}},
	volume = {19},
	issn = {09609822},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0960982209008860},
	doi = {10.1016/j.cub.2009.03.035},
	abstract = {Current views on multisensory motion integration assume separate substrates where visual motion perceptually dominates tactile motion [1, 2]. However, recent neuroimaging findings demonstrate strong activation of visual motion processing areas by tactile stimuli [3-6], implying a potentially bidirectional relationship. To test the relationship between visual and tactile motion processing, we examined the transfer of motion aftereffects. In the well-known visual motion aftereffect, adapting to visual motion in one direction causes a subsequently presented stationary stimulus to be perceived as moving in the opposite direction [7, 8]. The existence of motion aftereffects in the tactile domain was debated [9-11], though robust tactile motion aftereffects have recently been demonstrated [12, 13]. By using a motion adaptation paradigm, we found that repeated exposure to visual motion in a given direction produced a tactile motion aftereffect, the illusion of motion in the opponent direction across the finger pad. We also observed that repeated exposure to tactile motion induces a visual motion aftereffect, biasing the perceived direction of counterphase gratings. These crossmodal aftereffects, operating both from vision to touch and from touch to vision, present strong behavioral evidence that the processing of visual and tactile motion rely on shared representations that dynamically impact modality-specific perception.},
	language = {en},
	number = {9},
	urldate = {2020-03-12},
	journal = {Current Biology},
	author = {Konkle, Talia and Wang, Qi and Hayward, Vincent and Moore, Christopher I.},
	month = may,
	year = {2009},
	pages = {745--750},
	file = {Full Text:/Users/jjallen/Zotero/storage/74C89RME/Konkle et al. - 2009 - Motion Aftereffects Transfer between Touch and Vis.pdf:application/pdf}
}

Current views on multisensory motion integration assume separate substrates where visual motion perceptually dominates tactile motion [1, 2]. However, recent neuroimaging findings demonstrate strong activation of visual motion processing areas by tactile stimuli [3-6], implying a potentially bidirectional relationship. To test the relationship between visual and tactile motion processing, we examined the transfer of motion aftereffects. In the well-known visual motion aftereffect, adapting to visual motion in one direction causes a subsequently presented stationary stimulus to be perceived as moving in the opposite direction [7, 8]. The existence of motion aftereffects in the tactile domain was debated [9-11], though robust tactile motion aftereffects have recently been demonstrated [12, 13]. By using a motion adaptation paradigm, we found that repeated exposure to visual motion in a given direction produced a tactile motion aftereffect, the illusion of motion in the opponent direction across the finger pad. We also observed that repeated exposure to tactile motion induces a visual motion aftereffect, biasing the perceived direction of counterphase gratings. These crossmodal aftereffects, operating both from vision to touch and from touch to vision, present strong behavioral evidence that the processing of visual and tactile motion rely on shared representations that dynamically impact modality-specific perception.

@article{konkle_what_2009,
	title = {What can crossmodal aftereffects reveal about neural representation and dynamics?},
	volume = {2},
	issn = {1942-0889},
	url = {http://www.tandfonline.com/doi/abs/10.4161/cib.2.6.9344},
	doi = {10.4161/cib.2.6.9344},
	abstract = {The brain continuously adapts to incoming sensory stimuli, which can lead to perceptual illusions in the form of aftereffects. Recently we demonstrated that motion aftereffects transfer between vision and touch.(1) Here, the adapted brain state induced by one modality has consequences for processes in another modality, implying that somewhere in the processing stream, visual and tactile motion have shared underlying neural representations. We propose the adaptive processing hypothesis-any area that processes a stimulus adapts to the features of the stimulus it represents, and this adaptation has consequences for perception. This view argues that there is no single locus of an aftereffect. Rather, aftereffects emerge when the test stimulus used to probe the effect of adaptation requires processing of a given type. The illusion will reflect the properties of the brain area(s) that support that specific level of representation. We further suggest that many cortical areas are more process-dependent than modality-dependent, with crossmodal interactions reflecting shared processing demands in even 'early' sensory cortices.},
	language = {en},
	number = {6},
	urldate = {2020-03-12},
	journal = {Communicative \& Integrative Biology},
	author = {Konkle, Talia and Moore, Christopher I.},
	month = nov,
	year = {2009},
	pages = {479--481},
	file = {Full Text:/Users/jjallen/Zotero/storage/Q25YM4TH/Konkle and Moore - 2009 - What can crossmodal aftereffects reveal about neur.pdf:application/pdf}
}

The brain continuously adapts to incoming sensory stimuli, which can lead to perceptual illusions in the form of aftereffects. Recently we demonstrated that motion aftereffects transfer between vision and touch.(1) Here, the adapted brain state induced by one modality has consequences for processes in another modality, implying that somewhere in the processing stream, visual and tactile motion have shared underlying neural representations. We propose the adaptive processing hypothesis-any area that processes a stimulus adapts to the features of the stimulus it represents, and this adaptation has consequences for perception. This view argues that there is no single locus of an aftereffect. Rather, aftereffects emerge when the test stimulus used to probe the effect of adaptation requires processing of a given type. The illusion will reflect the properties of the brain area(s) that support that specific level of representation. We further suggest that many cortical areas are more process-dependent than modality-dependent, with crossmodal interactions reflecting shared processing demands in even 'early' sensory cortices.

@article{jones_quantitative_2009,
	title = {Quantitative {Analysis} and {Biophysically} {Realistic} {Neural} {Modeling} of the {MEG} {Mu} {Rhythm}: {Rhythmogenesis} and {Modulation} of {Sensory}-{Evoked} {Responses}},
	volume = {102},
	issn = {0022-3077, 1522-1598},
	shorttitle = {Quantitative {Analysis} and {Biophysically} {Realistic} {Neural} {Modeling} of the {MEG} {Mu} {Rhythm}},
	url = {https://www.physiology.org/doi/10.1152/jn.00535.2009},
	doi = {10.1152/jn.00535.2009},
	abstract = {Variations in cortical oscillations in the alpha (7–14 Hz) and beta (15–29 Hz) range have been correlated with attention, working memory, and stimulus detection. The mu rhythm recorded with magnetoencephalography (MEG) is a prominent oscillation generated by Rolandic cortex containing alpha and beta bands. Despite its prominence, the neural mechanisms regulating mu are unknown. We characterized the ongoing MEG mu rhythm from a localized source in the finger representation of primary somatosensory (SI) cortex. Subjects showed variation in the relative expression of mu-alpha or mu-beta, which were nonoverlapping for roughly 50\% of their respective durations on single trials. To delineate the origins of this rhythm, a biophysically principled computational neural model of SI was developed, with distinct laminae, inhibitory and excitatory neurons, and feedforward (FF, representative of lemniscal thalamic drive) and feedback (FB, representative of higher-order cortical drive or input from nonlemniscal thalamic nuclei) inputs defined by the laminar location of their postsynaptic effects. The mu-alpha component was accurately modeled by rhythmic FF input at approximately 10-Hz. The mu-beta component was accurately modeled by the addition of approximately 10-Hz FB input that was nearly synchronous with the FF input. The relative dominance of these two frequencies depended on the delay between FF and FB drives, their relative input strengths, and stochastic changes in these variables. The model also reproduced key features of the impact of high prestimulus mu power on peaks in SI-evoked activity. For stimuli presented during high mu power, the model predicted enhancement in an initial evoked peak and decreased subsequent deflections. In agreement, the MEG-evoked responses showed an enhanced initial peak and a trend to smaller subsequent peaks. These data provide new information on the dynamics of the mu rhythm in humans and the model provides a novel mechanistic interpretation of this rhythm and its functional significance.},
	language = {en},
	number = {6},
	urldate = {2020-03-12},
	journal = {Journal of Neurophysiology},
	author = {Jones, Stephanie R. and Pritchett, Dominique L. and Sikora, Michael A. and Stufflebeam, Steven M. and Hämäläinen, Matti and Moore, Christopher I.},
	month = dec,
	year = {2009},
	pages = {3554--3572},
	file = {Submitted Version:/Users/jjallen/Zotero/storage/KEU3DL5S/Jones et al. - 2009 - Quantitative Analysis and Biophysically Realistic .pdf:application/pdf}
}

Variations in cortical oscillations in the alpha (7–14 Hz) and beta (15–29 Hz) range have been correlated with attention, working memory, and stimulus detection. The mu rhythm recorded with magnetoencephalography (MEG) is a prominent oscillation generated by Rolandic cortex containing alpha and beta bands. Despite its prominence, the neural mechanisms regulating mu are unknown. We characterized the ongoing MEG mu rhythm from a localized source in the finger representation of primary somatosensory (SI) cortex. Subjects showed variation in the relative expression of mu-alpha or mu-beta, which were nonoverlapping for roughly 50% of their respective durations on single trials. To delineate the origins of this rhythm, a biophysically principled computational neural model of SI was developed, with distinct laminae, inhibitory and excitatory neurons, and feedforward (FF, representative of lemniscal thalamic drive) and feedback (FB, representative of higher-order cortical drive or input from nonlemniscal thalamic nuclei) inputs defined by the laminar location of their postsynaptic effects. The mu-alpha component was accurately modeled by rhythmic FF input at approximately 10-Hz. The mu-beta component was accurately modeled by the addition of approximately 10-Hz FB input that was nearly synchronous with the FF input. The relative dominance of these two frequencies depended on the delay between FF and FB drives, their relative input strengths, and stochastic changes in these variables. The model also reproduced key features of the impact of high prestimulus mu power on peaks in SI-evoked activity. For stimuli presented during high mu power, the model predicted enhancement in an initial evoked peak and decreased subsequent deflections. In agreement, the MEG-evoked responses showed an enhanced initial peak and a trend to smaller subsequent peaks. These data provide new information on the dynamics of the mu rhythm in humans and the model provides a novel mechanistic interpretation of this rhythm and its functional significance.

@article{cardin_driving_2009,
	title = {Driving fast-spiking cells induces gamma rhythm and controls sensory responses},
	volume = {459},
	issn = {0028-0836, 1476-4687},
	url = {http://www.nature.com/articles/nature08002},
	doi = {10.1038/nature08002},
	abstract = {Cortical gamma oscillations (20-80 Hz) predict increases in focused attention, and failure in gamma regulation is a hallmark of neurological and psychiatric disease. Current theory predicts that gamma oscillations are generated by synchronous activity of fast-spiking inhibitory interneurons, with the resulting rhythmic inhibition producing neural ensemble synchrony by generating a narrow window for effective excitation. We causally tested these hypotheses in barrel cortex in vivo by targeting optogenetic manipulation selectively to fast-spiking interneurons. Here we show that light-driven activation of fast-spiking interneurons at varied frequencies (8-200 Hz) selectively amplifies gamma oscillations. In contrast, pyramidal neuron activation amplifies only lower frequency oscillations, a cell-type-specific double dissociation. We found that the timing of a sensory input relative to a gamma cycle determined the amplitude and precision of evoked responses. Our data directly support the fast-spiking-gamma hypothesis and provide the first causal evidence that distinct network activity states can be induced in vivo by cell-type-specific activation.},
	language = {en},
	number = {7247},
	urldate = {2020-03-12},
	journal = {Nature},
	author = {Cardin, Jessica A. and Carlén, Marie and Meletis, Konstantinos and Knoblich, Ulf and Zhang, Feng and Deisseroth, Karl and Tsai, Li-Huei and Moore, Christopher I.},
	month = jun,
	year = {2009},
	pages = {663--667},
	file = {Accepted Version:/Users/jjallen/Zotero/storage/6XIEVP3N/Cardin et al. - 2009 - Driving fast-spiking cells induces gamma rhythm an.pdf:application/pdf}
}

Cortical gamma oscillations (20-80 Hz) predict increases in focused attention, and failure in gamma regulation is a hallmark of neurological and psychiatric disease. Current theory predicts that gamma oscillations are generated by synchronous activity of fast-spiking inhibitory interneurons, with the resulting rhythmic inhibition producing neural ensemble synchrony by generating a narrow window for effective excitation. We causally tested these hypotheses in barrel cortex in vivo by targeting optogenetic manipulation selectively to fast-spiking interneurons. Here we show that light-driven activation of fast-spiking interneurons at varied frequencies (8-200 Hz) selectively amplifies gamma oscillations. In contrast, pyramidal neuron activation amplifies only lower frequency oscillations, a cell-type-specific double dissociation. We found that the timing of a sensory input relative to a gamma cycle determined the amplitude and precision of evoked responses. Our data directly support the fast-spiking-gamma hypothesis and provide the first causal evidence that distinct network activity states can be induced in vivo by cell-type-specific activation.

@article{cao_pinacidil_2009,
	title = {Pinacidil induces vascular dilation and hyperemia in vivo and does not impact biophysical properties of neurons and astrocytes in vitro},
	volume = {76},
	issn = {0891-1150, 1939-2869},
	url = {https://www.mdedge.com/ccjm/article/95185/cardiology/pinacidil-induces-vascular-dilation-and-hyperemia-vivo-and-does-not},
	doi = {10.3949/ccjm.76.s2.16},
	abstract = {Vascular and neural systems are highly interdependent, as evidenced by the wealth of intrinsic modulators shared by the two systems. We tested the hypothesis that pinacidil, a selective agonist for the SUR2B receptor found on smooth muscles, could serve as an independent means of inducing vasodilation and increased local blood volume to emulate functional hyperemia. Application of pinacidil induced vasodilation and increased blood volume in the in vivo neocortex in anesthetized rats and awake mice. Direct application of this agent to the in vitro neocortical slice had no direct impact on biophysical properties of neurons or astrocytes assessed with whole-cell recording. These findings suggest that pinacidil provides an effective and selective means for inducing hyperemia in vivo, and may provide a useful tool in directly testing the impact of hemodynamics on neural activity, as recently predicted by the hemo-neural hypothesis.},
	language = {en},
	number = {Suppl\_2},
	urldate = {2020-03-12},
	journal = {Cleveland Clinic Journal of Medicine},
	author = {Cao, R. and Higashikubo, B. T. and Cardin, J. and Knoblich, U. and Ramos, R. and Nelson, M. T. and Moore, C. I and Brumberg, J. C.},
	month = apr,
	year = {2009},
	pages = {S80--S85},
	file = {Accepted Version:/Users/jjallen/Zotero/storage/G3EM5RA6/Cao et al. - 2009 - Pinacidil induces vascular dilation and hyperemia .pdf:application/pdf}
}

Vascular and neural systems are highly interdependent, as evidenced by the wealth of intrinsic modulators shared by the two systems. We tested the hypothesis that pinacidil, a selective agonist for the SUR2B receptor found on smooth muscles, could serve as an independent means of inducing vasodilation and increased local blood volume to emulate functional hyperemia. Application of pinacidil induced vasodilation and increased blood volume in the in vivo neocortex in anesthetized rats and awake mice. Direct application of this agent to the in vitro neocortical slice had no direct impact on biophysical properties of neurons or astrocytes assessed with whole-cell recording. These findings suggest that pinacidil provides an effective and selective means for inducing hyperemia in vivo, and may provide a useful tool in directly testing the impact of hemodynamics on neural activity, as recently predicted by the hemo-neural hypothesis.

@article{belmonte_autism_2009,
	title = {Autism {Overflows} with {Syntheses}},
	volume = {19},
	issn = {1040-7308, 1573-6660},
	url = {http://link.springer.com/10.1007/s11065-009-9099-9},
	doi = {10.1007/s11065-009-9099-9},
	language = {en},
	number = {2},
	urldate = {2020-03-12},
	journal = {Neuropsychology Review},
	author = {Belmonte, Matthew K. and Bonneh, Yoram S. and Adini, Yael and Iversen, Portia E. and Akshoomoff, Natacha A. and Kenet, Tal and Moore, Christopher I. and Simon, Helen J. and Houde, John F. and Merzenich, Michael M.},
	month = jun,
	year = {2009},
	pages = {273--274},
	file = {Submitted Version:/Users/jjallen/Zotero/storage/FJR29D9I/Belmonte et al. - 2009 - Autism Overflows with Syntheses.pdf:application/pdf}
}

@article{ritt_embodied_2008,
	title = {Embodied {Information} {Processing}: {Vibrissa} {Mechanics} and {Texture} {Features} {Shape} {Micromotions} in {Actively} {Sensing} {Rats}},
	volume = {57},
	issn = {08966273},
	shorttitle = {Embodied {Information} {Processing}},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0896627308000275},
	doi = {10.1016/j.neuron.2007.12.024},
	abstract = {Peripheral sensory organs provide the first transformation of sensory information, and understanding how their physical embodiment shapes transduction is central to understanding perception. We report the characterization of surface transduction during active sensing in the rodent vibrissa sensory system, a widely used model. Employing high-speed videography, we tracked vibrissae while rats sampled rough and smooth textures. Variation in vibrissa length predicted motion mean frequencies, including for the highest velocity events, indicating that biomechanics, such as vibrissa resonance, shape signals most likely to drive neural activity. Rough surface contact generated large amplitude, high-velocity "stick-slip-ring" events, while smooth surfaces generated smaller and more regular stick-slip oscillations. Both surfaces produced velocities exceeding those applied in reduced preparations, indicating active sensation of surfaces generates more robust drive than previously predicted. These findings demonstrate a key role for embodiment in vibrissal sensing and the importance of input transformations in sensory representation.},
	language = {en},
	number = {4},
	urldate = {2020-03-12},
	journal = {Neuron},
	author = {Ritt, Jason T. and Andermann, Mark L. and Moore, Christopher I.},
	month = feb,
	year = {2008},
	pages = {599--613},
	file = {Full Text:/Users/jjallen/Zotero/storage/J8BBTG5R/Ritt et al. - 2008 - Embodied Information Processing Vibrissa Mechanic.pdf:application/pdf}
}

Peripheral sensory organs provide the first transformation of sensory information, and understanding how their physical embodiment shapes transduction is central to understanding perception. We report the characterization of surface transduction during active sensing in the rodent vibrissa sensory system, a widely used model. Employing high-speed videography, we tracked vibrissae while rats sampled rough and smooth textures. Variation in vibrissa length predicted motion mean frequencies, including for the highest velocity events, indicating that biomechanics, such as vibrissa resonance, shape signals most likely to drive neural activity. Rough surface contact generated large amplitude, high-velocity "stick-slip-ring" events, while smooth surfaces generated smaller and more regular stick-slip oscillations. Both surfaces produced velocities exceeding those applied in reduced preparations, indicating active sensation of surfaces generates more robust drive than previously predicted. These findings demonstrate a key role for embodiment in vibrissal sensing and the importance of input transformations in sensory representation.

@article{moore_hemo-neural_2008,
	title = {The {Hemo}-{Neural} {Hypothesis}: {On} {The} {Role} of {Blood} {Flow} in {Information} {Processing}},
	volume = {99},
	issn = {0022-3077, 1522-1598},
	shorttitle = {The {Hemo}-{Neural} {Hypothesis}},
	url = {https://www.physiology.org/doi/10.1152/jn.01366.2006},
	doi = {10.1152/jn.01366.2006},
	abstract = {Brain vasculature is a complex and interconnected network under tight regulatory control that exists in intimate communication with neurons and glia. Typically, hemodynamics are considered to exclusively serve as a metabolic support system. In contrast to this canonical view, we propose that hemodynamics also play a role in information processing through modulation of neural activity. Functional hyperemia, the basis of the functional MRI (fMRI) BOLD signal, is a localized influx of blood correlated with neural activity levels. Functional hyperemia is considered by many to be excessive from a metabolic standpoint, but may be appropriate if interpreted as having an activity-dependent neuro-modulatory function. Hemodynamics may impact neural activity through direct and indirect mechanisms. Direct mechanisms include delivery of diffusible blood-borne messengers and mechanical and thermal modulation of neural activity. Indirect mechanisms are proposed to act through hemodynamic modulation of astrocytes, which can in turn regulate neural activity. These hemo-neural mechanisms should alter the information processing capacity of active local neural networks. Here, we focus on analysis of neocortical sensory processing. We predict that hemodynamics alter the gain of local cortical circuits, modulating the detection and discrimination of sensory stimuli. This novel view of information processing—that includes hemodynamics as an active and significant participant—has implications for understanding neural representation and the construction of accurate brain models. There are also potential medical benefits of an improved understanding of the role of hemodynamics in neural processing, as it directly bears on interpretation of and potential treatment for stroke, dementia, and epilepsy.},
	language = {en},
	number = {5},
	urldate = {2020-03-12},
	journal = {Journal of Neurophysiology},
	author = {Moore, Christopher I. and Cao, Rosa},
	month = may,
	year = {2008},
	pages = {2035--2047},
	file = {Accepted Version:/Users/jjallen/Zotero/storage/RWSFULI8/Moore and Cao - 2008 - The Hemo-Neural Hypothesis On The Role of Blood F.pdf:application/pdf}
}

Brain vasculature is a complex and interconnected network under tight regulatory control that exists in intimate communication with neurons and glia. Typically, hemodynamics are considered to exclusively serve as a metabolic support system. In contrast to this canonical view, we propose that hemodynamics also play a role in information processing through modulation of neural activity. Functional hyperemia, the basis of the functional MRI (fMRI) BOLD signal, is a localized influx of blood correlated with neural activity levels. Functional hyperemia is considered by many to be excessive from a metabolic standpoint, but may be appropriate if interpreted as having an activity-dependent neuro-modulatory function. Hemodynamics may impact neural activity through direct and indirect mechanisms. Direct mechanisms include delivery of diffusible blood-borne messengers and mechanical and thermal modulation of neural activity. Indirect mechanisms are proposed to act through hemodynamic modulation of astrocytes, which can in turn regulate neural activity. These hemo-neural mechanisms should alter the information processing capacity of active local neural networks. Here, we focus on analysis of neocortical sensory processing. We predict that hemodynamics alter the gain of local cortical circuits, modulating the detection and discrimination of sensory stimuli. This novel view of information processing—that includes hemodynamics as an active and significant participant—has implications for understanding neural representation and the construction of accurate brain models. There are also potential medical benefits of an improved understanding of the role of hemodynamics in neural processing, as it directly bears on interpretation of and potential treatment for stroke, dementia, and epilepsy.

@article{bonneh_cross-modal_2008,
	title = {Cross-modal extinction in a boy with severely autistic behaviour and high verbal intelligence},
	volume = {25},
	issn = {0264-3294, 1464-0627},
	url = {http://www.tandfonline.com/doi/abs/10.1080/02643290802106415},
	doi = {10.1080/02643290802106415},
	abstract = {Anecdotal reports from individuals with autism suggest a loss of awareness to stimuli from one modality in the presence of stimuli from another. Here we document such a case in a detailed study of A.M., a 13-year-old boy with autism in whom significant autistic behaviours are combined with an uneven IQ profile of superior verbal and low performance abilities. Although A.M.'s speech is often unintelligible, and his behaviour is dominated by motor stereotypies and impulsivity, he can communicate by typing or pointing independently within a letter board. A series of experiments using simple and highly salient visual, auditory, and tactile stimuli demonstrated a hierarchy of cross-modal extinction, in which auditory information extinguished other modalities at various levels of processing. A.M. also showed deficits in shifting and sustaining attention. These results provide evidence for monochannel perception in autism and suggest a general pattern of winner-takes-all processing in which a stronger stimulus-driven representation dominates behaviour, extinguishing weaker representations.},
	language = {en},
	number = {5},
	urldate = {2020-03-12},
	journal = {Cognitive Neuropsychology},
	author = {Bonneh, Yoram S. and Belmonte, Matthew K. and Pei, Francesca and Iversen, Portia E. and Kenet, Tal and Akshoomoff, Natacha and Adini, Yael and Simon, Helen J. and Moore, Christopher I. and Houde, John F. and Merzenich, Michael M.},
	month = jul,
	year = {2008},
	pages = {635--652},
	file = {Submitted Version:/Users/jjallen/Zotero/storage/B9PQE7UD/Bonneh et al. - 2008 - Cross-modal extinction in a boy with severely auti.pdf:application/pdf}
}

Anecdotal reports from individuals with autism suggest a loss of awareness to stimuli from one modality in the presence of stimuli from another. Here we document such a case in a detailed study of A.M., a 13-year-old boy with autism in whom significant autistic behaviours are combined with an uneven IQ profile of superior verbal and low performance abilities. Although A.M.'s speech is often unintelligible, and his behaviour is dominated by motor stereotypies and impulsivity, he can communicate by typing or pointing independently within a letter board. A series of experiments using simple and highly salient visual, auditory, and tactile stimuli demonstrated a hierarchy of cross-modal extinction, in which auditory information extinguished other modalities at various levels of processing. A.M. also showed deficits in shifting and sustaining attention. These results provide evidence for monochannel perception in autism and suggest a general pattern of winner-takes-all processing in which a stronger stimulus-driven representation dominates behaviour, extinguishing weaker representations.

@article{andermann_mechanical_2008,
	title = {Mechanical resonance enhances the sensitivity of the vibrissa sensory system to near-threshold stimuli},
	volume = {1235},
	issn = {00068993},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0006899308014522},
	doi = {10.1016/j.brainres.2008.06.054},
	abstract = {The representation of high-frequency sensory information is a crucial problem faced by the nervous system. Rodent facial vibrissae constitute a high-resolution sensory system, capable of discriminating and detecting subtle changes in tactual input. During active sensing, the mechanical properties of vibrissae may play a key role in filtering sensory information and translating it into neural activity. Previous studies have shown that rat vibrissae resonate, conferring frequency specificity to trigeminal ganglion (NV) and primary somatosensory cortex (SI) neurons during suprathreshold sensory stimulation. In addition to frequency specificity, a further potential impact of vibrissa resonance is enhancement of sensitivity to near-threshold stimuli through signal amplification. To examine the effect of resonance on peri-threshold inputs ({\textless}or=80 microm at the vibrissa tip), we recorded NV and SI neurons during stimulation at multiple amplitudes and frequencies, and generated minimal amplitude tuning curves. Several novel findings emerged from this study. First, vibrissa resonance significantly lowered the threshold for evoked neural activity, in many cases by an order of magnitude compared to stimuli presented at off-resonance frequencies. When stimulated at the fundamental resonance frequency, motions as small as 8 microm at the vibrissa tip, corresponding to angular deflections of less than 0.2 degrees, drove neural firing in the periphery and cortex. Second, a closer match between vibrissal and neural frequency tuning was found for lower amplitude motions. Third, simultaneous paired recordings demonstrated that the minimal amplitude of resonant vibrissa stimulation required to evoke responses in SI increased significantly for recordings outside the primary vibrissa barrel column, providing additional evidence for somatotopically localized frequency columns. These data demonstrate that resonant amplification can increase the sensitivity of the vibrissa sensory system to an ecologically relevant range of low-amplitude, high-frequency stimuli.},
	language = {en},
	urldate = {2020-03-12},
	journal = {Brain Research},
	author = {Andermann, M.L. and Moore, C.I.},
	month = oct,
	year = {2008},
	pages = {74--81},
	file = {Accepted Version:/Users/jjallen/Zotero/storage/NNTUYQAX/Andermann and Moore - 2008 - Mechanical resonance enhances the sensitivity of t.pdf:application/pdf}
}

The representation of high-frequency sensory information is a crucial problem faced by the nervous system. Rodent facial vibrissae constitute a high-resolution sensory system, capable of discriminating and detecting subtle changes in tactual input. During active sensing, the mechanical properties of vibrissae may play a key role in filtering sensory information and translating it into neural activity. Previous studies have shown that rat vibrissae resonate, conferring frequency specificity to trigeminal ganglion (NV) and primary somatosensory cortex (SI) neurons during suprathreshold sensory stimulation. In addition to frequency specificity, a further potential impact of vibrissa resonance is enhancement of sensitivity to near-threshold stimuli through signal amplification. To examine the effect of resonance on peri-threshold inputs (\textlessor=80 microm at the vibrissa tip), we recorded NV and SI neurons during stimulation at multiple amplitudes and frequencies, and generated minimal amplitude tuning curves. Several novel findings emerged from this study. First, vibrissa resonance significantly lowered the threshold for evoked neural activity, in many cases by an order of magnitude compared to stimuli presented at off-resonance frequencies. When stimulated at the fundamental resonance frequency, motions as small as 8 microm at the vibrissa tip, corresponding to angular deflections of less than 0.2 degrees, drove neural firing in the periphery and cortex. Second, a closer match between vibrissal and neural frequency tuning was found for lower amplitude motions. Third, simultaneous paired recordings demonstrated that the minimal amplitude of resonant vibrissa stimulation required to evoke responses in SI increased significantly for recordings outside the primary vibrissa barrel column, providing additional evidence for somatotopically localized frequency columns. These data demonstrate that resonant amplification can increase the sensitivity of the vibrissa sensory system to an ecologically relevant range of low-amplitude, high-frequency stimuli.

@article{kerr_cortical_2007,
	title = {Cortical {Dynamics} {As} {A} {Therapeutic} {Mechanism} for {Touch} {Healing}},
	volume = {13},
	issn = {1075-5535, 1557-7708},
	url = {http://www.liebertpub.com/doi/10.1089/acm.2006.5245},
	doi = {10.1089/acm.2006.5245},
	abstract = {Touch Healing (TH) therapies, defined here as treatments whose primary route of administration is tactile contact and/or active guiding of somatic attention, are ubiquitous across cultures. Despite increasing integration of TH into mainstream medicine through therapies such as Reiki, Therapeutic Touch,(TM) and somatically focused meditation practices such as Mindfulness-Based Stress Reduction, relatively little is known about potential underlying mechanisms. Here, we present a neuroscientific explanation for the prevalence and effectiveness of TH therapies for relieving chronic pain. We begin with a cross-cultural review of several different types of TH treatments and identify common characteristics, including: light tactile contact and/or a somatosensory attention directed toward the body, a behaviorally relevant context, a relaxed context and repeated treatment sessions. These cardinal features are also key elements of established mechanisms of neural plasticity in somatosensory cortical maps, suggesting that sensory reorganization is a mechanism for the healing observed. Consideration of the potential health benefits of meditation practice specifically suggests that these practices provide training in the regulation of neural and perceptual dynamics that provide ongoing resistance to the development of maladaptive somatic representations. This model provides several direct predictions for investigating ways that TH may induce cortical plasticity and dynamics in pain remediation.},
	language = {en},
	number = {1},
	urldate = {2020-03-16},
	journal = {The Journal of Alternative and Complementary Medicine},
	author = {Kerr, Catherine E. and Wasserman, Rachel H. and Moore, Christopher I.},
	month = jan,
	year = {2007},
	pages = {59--66},
	file = {Submitted Version:/Users/jjallen/Zotero/storage/4SZ2535L/Kerr et al. - 2007 - Cortical Dynamics As A Therapeutic Mechanism for T.pdf:application/pdf}
}

Touch Healing (TH) therapies, defined here as treatments whose primary route of administration is tactile contact and/or active guiding of somatic attention, are ubiquitous across cultures. Despite increasing integration of TH into mainstream medicine through therapies such as Reiki, Therapeutic Touch,(TM) and somatically focused meditation practices such as Mindfulness-Based Stress Reduction, relatively little is known about potential underlying mechanisms. Here, we present a neuroscientific explanation for the prevalence and effectiveness of TH therapies for relieving chronic pain. We begin with a cross-cultural review of several different types of TH treatments and identify common characteristics, including: light tactile contact and/or a somatosensory attention directed toward the body, a behaviorally relevant context, a relaxed context and repeated treatment sessions. These cardinal features are also key elements of established mechanisms of neural plasticity in somatosensory cortical maps, suggesting that sensory reorganization is a mechanism for the healing observed. Consideration of the potential health benefits of meditation practice specifically suggests that these practices provide training in the regulation of neural and perceptual dynamics that provide ongoing resistance to the development of maladaptive somatic representations. This model provides several direct predictions for investigating ways that TH may induce cortical plasticity and dynamics in pain remediation.

@article{jones_neural_2007,
	title = {Neural {Correlates} of {Tactile} {Detection}: {A} {Combined} {Magnetoencephalography} and {Biophysically} {Based} {Computational} {Modeling} {Study}},
	volume = {27},
	issn = {0270-6474, 1529-2401},
	shorttitle = {Neural {Correlates} of {Tactile} {Detection}},
	url = {http://www.jneurosci.org/cgi/doi/10.1523/JNEUROSCI.0482-07.2007},
	doi = {10.1523/JNEUROSCI.0482-07.2007},
	abstract = {Previous reports conflict as to the role of primary somatosensory neocortex (SI) in tactile detection. We addressed this question in normal human subjects using whole-head magnetoencephalography (MEG) recording. We found that the evoked signal (0-175 ms) showed a prominent equivalent current dipole that localized to the anterior bank of the postcentral gyrus, area 3b of SI. The magnitude and timing of peaks in the SI waveform were stimulus amplitude dependent and predicted perception beginning at approximately 70 ms after stimulus. To make a direct and principled connection between the SI waveform and underlying neural dynamics, we developed a biophysically realistic computational SI model that contained excitatory and inhibitory neurons in supragranular and infragranular layers. The SI evoked response was successfully reproduced from the intracellular currents in pyramidal neurons driven by a sequence of lamina-specific excitatory input, consisting of output from the granular layer (approximately 25 ms), exogenous input to the supragranular layers (approximately 70 ms), and a second wave of granular output (approximately 135 ms). The model also predicted that SI correlates of perception reflect stronger and shorter-latency supragranular and late granular drive during perceived trials. These findings strongly support the view that signatures of tactile detection are present in human SI and are mediated by local neural dynamics induced by lamina-specific synaptic drive. Furthermore, our model provides a biophysically realistic solution to the MEG signal and can predict the electrophysiological correlates of human perception.},
	language = {en},
	number = {40},
	urldate = {2020-03-16},
	journal = {Journal of Neuroscience},
	author = {Jones, S. R. and Pritchett, D. L. and Stufflebeam, S. M. and Hamalainen, M. and Moore, C. I.},
	month = oct,
	year = {2007},
	pages = {10751--10764},
	file = {Full Text:/Users/jjallen/Zotero/storage/YUUMCMZR/Jones et al. - 2007 - Neural Correlates of Tactile Detection A Combined.pdf:application/pdf}
}

Previous reports conflict as to the role of primary somatosensory neocortex (SI) in tactile detection. We addressed this question in normal human subjects using whole-head magnetoencephalography (MEG) recording. We found that the evoked signal (0-175 ms) showed a prominent equivalent current dipole that localized to the anterior bank of the postcentral gyrus, area 3b of SI. The magnitude and timing of peaks in the SI waveform were stimulus amplitude dependent and predicted perception beginning at approximately 70 ms after stimulus. To make a direct and principled connection between the SI waveform and underlying neural dynamics, we developed a biophysically realistic computational SI model that contained excitatory and inhibitory neurons in supragranular and infragranular layers. The SI evoked response was successfully reproduced from the intracellular currents in pyramidal neurons driven by a sequence of lamina-specific excitatory input, consisting of output from the granular layer (approximately 25 ms), exogenous input to the supragranular layers (approximately 70 ms), and a second wave of granular output (approximately 135 ms). The model also predicted that SI correlates of perception reflect stronger and shorter-latency supragranular and late granular drive during perceived trials. These findings strongly support the view that signatures of tactile detection are present in human SI and are mediated by local neural dynamics induced by lamina-specific synaptic drive. Furthermore, our model provides a biophysically realistic solution to the MEG signal and can predict the electrophysiological correlates of human perception.

@article{schaechter_structural_2006,
	title = {Structural and functional plasticity in the somatosensory cortex of chronic stroke patients},
	volume = {129},
	issn = {0006-8950, 1460-2156},
	url = {https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/awl214},
	doi = {10.1093/brain/awl214},
	abstract = {Animal studies have demonstrated that motor recovery after hemiparetic stroke is associated with functional and structural brain plasticity. While studies in stroke patients have revealed functional plasticity in sensorimotor cortical areas in association with motor recovery, corresponding structural plasticity has not been shown. We sought to test the hypothesis that chronic hemiparetic stroke patients exhibit structural plasticity in the same sensorimotor cortical areas that exhibit functional plasticity. Functional MRI during unilateral tactile stimulation and structural MRI was conducted in chronic stroke patients and normal subjects. Using recently developed computational methods for high-resolution analysis of MRI data, we evaluated for between-group differences in functional activation responses, and cortical thickness of areas that showed an enhanced activation response in the patients. We found a significant (P {\textless} 0.005) increase in the activation response in areas of the ventral postcentral gyrus (POG) in the patients relative to controls. These same ventral POG areas showed a significant (P {\textless} 0.05) increase in cortical thickness in the patients. Control cortical areas did not show a significant between-group difference in thickness or activation response. These results provide the first evidence of structural plasticity co-localized with areas exhibiting functional plasticity in the human brain after stroke.},
	language = {en},
	number = {10},
	urldate = {2020-03-16},
	journal = {Brain},
	author = {Schaechter, J. D.},
	month = jul,
	year = {2006},
	pages = {2722--2733},
	file = {Full Text:/Users/jjallen/Zotero/storage/3YH8Q7PD/Schaechter - 2006 - Structural and functional plasticity in the somato.pdf:application/pdf}
}

Animal studies have demonstrated that motor recovery after hemiparetic stroke is associated with functional and structural brain plasticity. While studies in stroke patients have revealed functional plasticity in sensorimotor cortical areas in association with motor recovery, corresponding structural plasticity has not been shown. We sought to test the hypothesis that chronic hemiparetic stroke patients exhibit structural plasticity in the same sensorimotor cortical areas that exhibit functional plasticity. Functional MRI during unilateral tactile stimulation and structural MRI was conducted in chronic stroke patients and normal subjects. Using recently developed computational methods for high-resolution analysis of MRI data, we evaluated for between-group differences in functional activation responses, and cortical thickness of areas that showed an enhanced activation response in the patients. We found a significant (P \textless 0.005) increase in the activation response in areas of the ventral postcentral gyrus (POG) in the patients relative to controls. These same ventral POG areas showed a significant (P \textless 0.05) increase in cortical thickness in the patients. Control cortical areas did not show a significant between-group difference in thickness or activation response. These results provide the first evidence of structural plasticity co-localized with areas exhibiting functional plasticity in the human brain after stroke.

@article{haslinger_analysis_2006,
	title = {Analysis of {LFP} {Phase} {Predicts} {Sensory} {Response} of {Barrel} {Cortex}},
	volume = {96},
	issn = {0022-3077, 1522-1598},
	url = {https://www.physiology.org/doi/10.1152/jn.01288.2005},
	doi = {10.1152/jn.01288.2005},
	abstract = {Several previous studies have shown the existence of Up and Down states and have linked their magnitude (e.g., depolarization level) to the size of sensory-evoked responses. Here, we studied how the temporal dynamics of such states influence the sensory-evoked response to vibrissa deflection. Under α-chloralose anesthesia, barrel cortex exhibits strong quasi-periodic ∼1-Hz local field potential (LFP) oscillations generated by the synchronized fluctuation of large populations of neurons between depolarized (Up) and hyperpolarized (Down) states. Using a linear depth electrode array, we recorded the LFP and multiunit activity (MUA) simultaneously across multiple layers of the barrel column and used the LFP to approximate the subthreshold Up–Down fluctuations. Our central finding is that the MUA response is a strong function of the LFP oscillation’s phase. When only ongoing LFP magnitude was considered, the response was largest in the Down state, in agreement with previous studies. However, consideration of the LFP phase revealed that the MUA response varied smoothly as a function of LFP phase in a manner that was not monotonically dependent on LFP magnitude. The LFP phase is therefore a better predictor of the MUA response than the LFP magnitude is. Our results suggest that, in the presence of ongoing oscillations, there can be a continuum of response properties and that each phase may, at times, need to be considered a distinct cortical state.},
	language = {en},
	number = {3},
	urldate = {2020-03-16},
	journal = {Journal of Neurophysiology},
	author = {Haslinger, R. and Ulbert, I. and Moore, C. I. and Brown, E. N. and Devor, A.},
	month = sep,
	year = {2006},
	pages = {1658--1663},
	file = {Submitted Version:/Users/jjallen/Zotero/storage/3W6WME9X/Haslinger et al. - 2006 - Analysis of LFP Phase Predicts Sensory Response of.pdf:application/pdf}
}

Several previous studies have shown the existence of Up and Down states and have linked their magnitude (e.g., depolarization level) to the size of sensory-evoked responses. Here, we studied how the temporal dynamics of such states influence the sensory-evoked response to vibrissa deflection. Under α-chloralose anesthesia, barrel cortex exhibits strong quasi-periodic ∼1-Hz local field potential (LFP) oscillations generated by the synchronized fluctuation of large populations of neurons between depolarized (Up) and hyperpolarized (Down) states. Using a linear depth electrode array, we recorded the LFP and multiunit activity (MUA) simultaneously across multiple layers of the barrel column and used the LFP to approximate the subthreshold Up–Down fluctuations. Our central finding is that the MUA response is a strong function of the LFP oscillation’s phase. When only ongoing LFP magnitude was considered, the response was largest in the Down state, in agreement with previous studies. However, consideration of the LFP phase revealed that the MUA response varied smoothly as a function of LFP phase in a manner that was not monotonically dependent on LFP magnitude. The LFP phase is therefore a better predictor of the MUA response than the LFP magnitude is. Our results suggest that, in the presence of ongoing oscillations, there can be a continuum of response properties and that each phase may, at times, need to be considered a distinct cortical state.

@article{andermann_somatotopic_2006,
	title = {A somatotopic map of vibrissa motion direction within a barrel column},
	volume = {9},
	issn = {1097-6256, 1546-1726},
	url = {http://www.nature.com/articles/nn1671},
	doi = {10.1038/nn1671},
	abstract = {Most mammals possess high-resolution visual perception, with primary visual cortices containing fine-scale, inter-related feature representations (for example, orientation and ocular dominance). Rats lack precise vision, but their vibrissa sensory system provides a precise tactile modality, including vibrissa-related 'barrel' columns in primary somatosensory cortex. Here, we examined the subcolumnar organization of direction preference and somatotopy using a new omni-directional, multi-vibrissa stimulator. We discovered a direction map that was systematically linked to somatotopy, such that neurons were tuned for motion toward their preferred surround vibrissa. This sub-barrel column direction map demonstrated an emergent refinement from layer IV to layer II/III. These data suggest that joint processing of multiple sensory features is a common property of high-resolution sensory systems.},
	language = {en},
	number = {4},
	urldate = {2020-03-16},
	journal = {Nature Neuroscience},
	author = {Andermann, Mark L and Moore, Christopher I},
	month = apr,
	year = {2006},
	pages = {543--551}
}

Most mammals possess high-resolution visual perception, with primary visual cortices containing fine-scale, inter-related feature representations (for example, orientation and ocular dominance). Rats lack precise vision, but their vibrissa sensory system provides a precise tactile modality, including vibrissa-related 'barrel' columns in primary somatosensory cortex. Here, we examined the subcolumnar organization of direction preference and somatotopy using a new omni-directional, multi-vibrissa stimulator. We discovered a direction map that was systematically linked to somatotopy, such that neurons were tuned for motion toward their preferred surround vibrissa. This sub-barrel column direction map demonstrated an emergent refinement from layer IV to layer II/III. These data suggest that joint processing of multiple sensory features is a common property of high-resolution sensory systems.

@article{lazar_meditation_2005,
	title = {Meditation experience is associated with increased cortical thickness:},
	volume = {16},
	issn = {0959-4965},
	shorttitle = {Meditation experience is associated with increased cortical thickness},
	url = {http://journals.lww.com/00001756-200511280-00005},
	doi = {10.1097/01.wnr.0000186598.66243.19},
	abstract = {Previous research indicates that long-term meditation practice is associated with altered resting electroencephalogram patterns, suggestive of long lasting changes in brain activity. We hypothesized that meditation practice might also be associated with changes in the brain's physical structure. Magnetic resonance imaging was used to assess cortical thickness in 20 participants with extensive Insight meditation experience, which involves focused attention to internal experiences. Brain regions associated with attention, interoception and sensory processing were thicker in meditation participants than matched controls, including the prefrontal cortex and right anterior insula. Between-group differences in prefrontal cortical thickness were most pronounced in older participants, suggesting that meditation might offset age-related cortical thinning. Finally, the thickness of two regions correlated with meditation experience. These data provide the first structural evidence for experience-dependent cortical plasticity associated with meditation practice.},
	language = {en},
	number = {17},
	urldate = {2020-03-16},
	journal = {NeuroReport},
	author = {Lazar, Sara W. and Kerr, Catherine E. and Wasserman, Rachel H. and Gray, Jeremy R. and Greve, Douglas N. and Treadway, Michael T. and McGarvey, Metta and Quinn, Brian T. and Dusek, Jeffery A. and Benson, Herbert and Rauch, Scott L. and Moore, Christopher I. and Fischl, Bruce},
	month = nov,
	year = {2005},
	pages = {1893--1897},
	file = {Accepted Version:/Users/jjallen/Zotero/storage/HKYQ96VN/Lazar et al. - 2005 - Meditation experience is associated with increased.pdf:application/pdf}
}

Previous research indicates that long-term meditation practice is associated with altered resting electroencephalogram patterns, suggestive of long lasting changes in brain activity. We hypothesized that meditation practice might also be associated with changes in the brain's physical structure. Magnetic resonance imaging was used to assess cortical thickness in 20 participants with extensive Insight meditation experience, which involves focused attention to internal experiences. Brain regions associated with attention, interoception and sensory processing were thicker in meditation participants than matched controls, including the prefrontal cortex and right anterior insula. Between-group differences in prefrontal cortical thickness were most pronounced in older participants, suggesting that meditation might offset age-related cortical thinning. Finally, the thickness of two regions correlated with meditation experience. These data provide the first structural evidence for experience-dependent cortical plasticity associated with meditation practice.

@article{moore_frequency-dependent_2004,
	title = {Frequency-{Dependent} {Processing} in the {Vibrissa} {Sensory} {System}},
	volume = {91},
	issn = {0022-3077, 1522-1598},
	url = {https://www.physiology.org/doi/10.1152/jn.00925.2003},
	doi = {10.1152/jn.00925.2003},
	abstract = {The vibrissa sensory system is a key model for investigating principles of sensory processing. Specific frequency ranges of vibrissa motion, generated by rodent sensory behaviors (e.g., active exploration or resting) and by stimulus features, characterize perception by this system. During active exploration, rats typically sweep their vibrissae at ∼4–12 Hz against and over tactual surfaces, and during rest or quiescence, their vibrissae are typically still ({\textless}1 Hz). When a vibrissa is swept over an object, microgeometric surface features (e.g., grains on sandpaper) likely create higher frequency vibrissa vibrations that are greater than or equal to several hundred Hertz. In this article, I first review thalamic and cortical neural responses to vibrissa stimulation at 1–40 Hz. I then propose that neural dynamics optimize the detection of stimuli in low-frequency contexts (e.g., 1 Hz) and the discrimination of stimuli in the whisking frequency range. In the third section, I describe how the intrinsic biomechanical properties of vibrissae, their ability to resonate when stimulated at specific frequencies, may promote detection and discrimination of high-frequency inputs, including textured surfaces. In the final section, I hypothesize that distinct low- and high-frequency processing modes may exist in the somatosensory cortex (SI), such that neural responses to stimuli at 1–40 Hz do not necessarily predict responses to higher frequency inputs. In total, these studies show that several frequency-specific mechanisms impact information transmission in the vibrissa sensory system and suggest that these properties play a crucial role in perception.},
	language = {en},
	number = {6},
	urldate = {2020-03-16},
	journal = {Journal of Neurophysiology},
	author = {Moore, Christopher I.},
	month = jun,
	year = {2004},
	pages = {2390--2399},
	file = {Full Text:/Users/jjallen/Zotero/storage/6FBKZET4/Moore - 2004 - Frequency-Dependent Processing in the Vibrissa Sen.pdf:application/pdf}
}

The vibrissa sensory system is a key model for investigating principles of sensory processing. Specific frequency ranges of vibrissa motion, generated by rodent sensory behaviors (e.g., active exploration or resting) and by stimulus features, characterize perception by this system. During active exploration, rats typically sweep their vibrissae at ∼4–12 Hz against and over tactual surfaces, and during rest or quiescence, their vibrissae are typically still (\textless1 Hz). When a vibrissa is swept over an object, microgeometric surface features (e.g., grains on sandpaper) likely create higher frequency vibrissa vibrations that are greater than or equal to several hundred Hertz. In this article, I first review thalamic and cortical neural responses to vibrissa stimulation at 1–40 Hz. I then propose that neural dynamics optimize the detection of stimuli in low-frequency contexts (e.g., 1 Hz) and the discrimination of stimuli in the whisking frequency range. In the third section, I describe how the intrinsic biomechanical properties of vibrissae, their ability to resonate when stimulated at specific frequencies, may promote detection and discrimination of high-frequency inputs, including textured surfaces. In the final section, I hypothesize that distinct low- and high-frequency processing modes may exist in the somatosensory cortex (SI), such that neural responses to stimuli at 1–40 Hz do not necessarily predict responses to higher frequency inputs. In total, these studies show that several frequency-specific mechanisms impact information transmission in the vibrissa sensory system and suggest that these properties play a crucial role in perception.

@article{andermann_neural_2004,
	title = {Neural {Correlates} of {Vibrissa} {Resonance}},
	volume = {42},
	issn = {08966273},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0896627304001989},
	doi = {10.1016/S0896-6273(04)00198-9},
	abstract = {The array of vibrissae on a rat's face is the first stage of a high-resolution tactile sensing system. Recently, it was discovered that vibrissae (whiskers) resonate when stimulated at specific frequencies, generating several-fold increases in motion amplitude. We investigated the neural correlates of vibrissa resonance in trigeminal ganglion and primary somatosensory cortex (SI) neurons (regular and fast spiking units) by presenting low-amplitude, high-frequency vibrissa stimulation. We found that somatosensory neurons showed band-pass tuning and enhanced sensitivity to small amplitude stimuli, reflecting the resonance amplification of vibrissa motion. Further, a putative somatotopic map of frequency selectivity was observed in SI, with isofrequency columns extending along the representations of arcs of vibrissae, in agreement with the gradient in vibrissa resonance across the vibrissa pad. These findings suggest several parallels between frequency processing in the vibrissa system and the auditory system and have important implications for detection and discrimination of tactile information.},
	language = {en},
	number = {3},
	urldate = {2020-03-16},
	journal = {Neuron},
	author = {Andermann, Mark L and Ritt, Jason and Neimark, Maria A and Moore, Christopher I},
	month = may,
	year = {2004},
	pages = {451--463}
}

The array of vibrissae on a rat's face is the first stage of a high-resolution tactile sensing system. Recently, it was discovered that vibrissae (whiskers) resonate when stimulated at specific frequencies, generating several-fold increases in motion amplitude. We investigated the neural correlates of vibrissa resonance in trigeminal ganglion and primary somatosensory cortex (SI) neurons (regular and fast spiking units) by presenting low-amplitude, high-frequency vibrissa stimulation. We found that somatosensory neurons showed band-pass tuning and enhanced sensitivity to small amplitude stimuli, reflecting the resonance amplification of vibrissa motion. Further, a putative somatotopic map of frequency selectivity was observed in SI, with isofrequency columns extending along the representations of arcs of vibrissae, in agreement with the gradient in vibrissa resonance across the vibrissa pad. These findings suggest several parallels between frequency processing in the vibrissa system and the auditory system and have important implications for detection and discrimination of tactile information.

@article{neimark_vibrissa_2003,
	title = {Vibrissa resonance as a transduction mechanism for tactile encoding},
	volume = {23},
	issn = {1529-2401},
	abstract = {We present evidence that resonance properties of rat vibrissae differentially amplify high-frequency and complex tactile signals. Consistent with a model of vibrissa mechanics, optical measurements of vibrissae revealed that their first mechanical resonance frequencies systematically varied from low (60-100 Hz) in longer, posterior vibrissae to high ( approximately 750 Hz) in shorter, anterior vibrissae. Resonance amplification of tactile input was observed in vivo and ex vivo, and in a variety of boundary conditions that are likely to occur during perception, including stimulation of the vibrissa with moving complex natural stimuli such as sandpaper. Vibrissae were underdamped, allowing for sharp tuning to resonance frequencies. Vibrissa resonance constitutes a potentially useful mechanism for perception of high-frequency and complex tactile signals. Amplification of small amplitude signals by resonance could facilitate detection of stimuli that would otherwise fail to drive neural activity. The systematic map of frequency sensitivity across the face could facilitate texture discrimination through somatotopic encoding of frequency content. These findings suggest strong parallels between vibrissa tactile processing and auditory encoding, in which the cochlea also uses resonance to amplify low-amplitude signals and to generate a spatial map of frequency sensitivity.},
	language = {eng},
	number = {16},
	journal = {The Journal of Neuroscience: The Official Journal of the Society for Neuroscience},
	author = {Neimark, Maria A. and Andermann, Mark L. and Hopfield, John J. and Moore, Christopher I.},
	month = jul,
	year = {2003},
	pmid = {12878691},
	pmcid = {PMC6740638},
	keywords = {Animals, Biological Clocks, Biophysical Phenomena, Biophysics, Discrimination, Psychological, In Vitro Techniques, Models, Biological, Physical Stimulation, Predictive Value of Tests, Rats, Reproducibility of Results, Surface Properties, Touch, Vibration, Vibrissae},
	pages = {6499--6509}
}

We present evidence that resonance properties of rat vibrissae differentially amplify high-frequency and complex tactile signals. Consistent with a model of vibrissa mechanics, optical measurements of vibrissae revealed that their first mechanical resonance frequencies systematically varied from low (60-100 Hz) in longer, posterior vibrissae to high ( approximately 750 Hz) in shorter, anterior vibrissae. Resonance amplification of tactile input was observed in vivo and ex vivo, and in a variety of boundary conditions that are likely to occur during perception, including stimulation of the vibrissa with moving complex natural stimuli such as sandpaper. Vibrissae were underdamped, allowing for sharp tuning to resonance frequencies. Vibrissa resonance constitutes a potentially useful mechanism for perception of high-frequency and complex tactile signals. Amplification of small amplitude signals by resonance could facilitate detection of stimuli that would otherwise fail to drive neural activity. The systematic map of frequency sensitivity across the face could facilitate texture discrimination through somatotopic encoding of frequency content. These findings suggest strong parallels between vibrissa tactile processing and auditory encoding, in which the cochlea also uses resonance to amplify low-amplitude signals and to generate a spatial map of frequency sensitivity.

@article{garabedian_band-pass_2003,
	title = {Band-{Pass} {Response} {Properties} of {Rat} {SI} {Neurons}},
	volume = {90},
	issn = {0022-3077, 1522-1598},
	url = {https://www.physiology.org/doi/10.1152/jn.01158.2002},
	doi = {10.1152/jn.01158.2002},
	abstract = {Rats typically employ 4- to 12-Hz “whisking” movements of their vibrissae during tactile exploration. The intentional sampling of signals in this frequency range suggests that neural processing of tactile information may be differentially engaged in this bandwidth. We examined action potential responses in rat primary somatosensory cortex (SI) to a range of frequencies of vibrissa motion. Single vibrissae were mechanically deflected with 5-s pulse trains at rates ≤40 Hz. As previously reported, vibrissa deflection evoked robust neural responses that consistently adapted to stimulus rates ≥3 Hz. In contrast with this low-pass feature of the response, several other characteristics of the response revealed bandpass response properties. While average evoked response amplitudes measured 0–35 ms after stimulus onset typically decreased with increasing frequency, the later components of the response ({\textgreater}15 ms post stimulus) were augmented at frequencies between 3 and 10 Hz. Further, during the steady state, both rate and temporal measures of neural activity, measured as total spike rate or vector strength (a measure of temporal fidelity of spike timing across cycles), showed peak signal values at 5–10 Hz. A minimal biophysical network model of SI layer IV, consisting of an excitatory and inhibitory neuron and thalamocortical input, captured the spike rate and vector strength band-pass characteristics. Further analyses in which specific elements were selectively removed from the model suggest that slow inhibitory influences give rise to the band-pass peak in temporal precision, while thalamocortical adaptation can account for the band-pass peak in spike rate. The presence of these band-pass characteristics may be a general property of thalamocortical circuits that lead rodents to target this frequency range with their whisking behavior.},
	language = {en},
	number = {3},
	urldate = {2020-03-16},
	journal = {Journal of Neurophysiology},
	author = {Garabedian, Catherine E. and Jones, Stephanie R. and Merzenich, Michael M. and Dale, Anders and Moore, Christopher I.},
	month = sep,
	year = {2003},
	pages = {1379--1391},
	file = {Submitted Version:/Users/jjallen/Zotero/storage/SNGZG8TE/Garabedian et al. - 2003 - Band-Pass Response Properties of Rat SI Neurons.pdf:application/pdf}
}

Rats typically employ 4- to 12-Hz “whisking” movements of their vibrissae during tactile exploration. The intentional sampling of signals in this frequency range suggests that neural processing of tactile information may be differentially engaged in this bandwidth. We examined action potential responses in rat primary somatosensory cortex (SI) to a range of frequencies of vibrissa motion. Single vibrissae were mechanically deflected with 5-s pulse trains at rates ≤40 Hz. As previously reported, vibrissa deflection evoked robust neural responses that consistently adapted to stimulus rates ≥3 Hz. In contrast with this low-pass feature of the response, several other characteristics of the response revealed bandpass response properties. While average evoked response amplitudes measured 0–35 ms after stimulus onset typically decreased with increasing frequency, the later components of the response (\textgreater15 ms post stimulus) were augmented at frequencies between 3 and 10 Hz. Further, during the steady state, both rate and temporal measures of neural activity, measured as total spike rate or vector strength (a measure of temporal fidelity of spike timing across cycles), showed peak signal values at 5–10 Hz. A minimal biophysical network model of SI layer IV, consisting of an excitatory and inhibitory neuron and thalamocortical input, captured the spike rate and vector strength band-pass characteristics. Further analyses in which specific elements were selectively removed from the model suggest that slow inhibitory influences give rise to the band-pass peak in temporal precision, while thalamocortical adaptation can account for the band-pass peak in spike rate. The presence of these band-pass characteristics may be a general property of thalamocortical circuits that lead rodents to target this frequency range with their whisking behavior.

@article{moore_segregation_2000,
	title = {Segregation of {Somatosensory} {Activation} in the {Human} {Rolandic} {Cortex} {Using} {fMRI}},
	volume = {84},
	issn = {0022-3077, 1522-1598},
	url = {http://www.physiology.org/doi/10.1152/jn.2000.84.1.558},
	doi = {10.1152/jn.2000.84.1.558},
	abstract = {The segregation of sensory information into distinct cortical areas is an important organizational feature of mammalian sensory systems. Here, we provide functional magnetic resonance imaging (fMRI) evidence for the functional delineation of somatosensory representations in the human central sulcus region. Data were collected with a 3-Tesla scanner during two stimulation protocols, a punctate tactile condition without a kinesthetic/motor component, and a kinesthetic/motor condition without a punctate tactile component. With three-dimensional (3-D) anatomical reconstruction techniques, we analyzed data in individual subjects, using the pattern of activation and the anatomical position of specific cortical areas to guide the analysis. As a complimentary analysis, we used a brain averaging technique that emphasized the similarity of cortical features in the morphing of individual subjects and thereby minimized the distortion of the location of cortical activation sites across individuals. A primary finding of this study was differential activation of the cortex on the fundus of the central sulcus, the position of area 3a, during the two tasks. Punctate tactile stimulation of the palm, administered at 3 Hz with a 5.88(log10.mg) von Frey filament, activated discrete regions within the precentral (PreCG) and postcentral (PoCG) gyri, corresponding to areas 6, 3b, 1, and 2, but did not activate area 3a. Conversely, kinesthetic/motor stimulation, 3-Hz flexion and extension of the digits, activated area 3a, the PreCG (areas 6 and 4), and the PoCG (areas 3b, 1, and 2). These activation patterns were observed in individual subjects and in the averaged data, providing strong evidence for the existence of a distinct representation within area 3a in humans. The percentage signal changes in the PreCG and PoCG regions activated by tactile stimulation, and in the intervening gap region, support this functional dissociation. In addition to this distinction within the fundus of the central sulcus, the combination of high-resolution imaging and 3-D analysis techniques permitted localization of activation within areas 6, 4, 3a, 3b, 1, and 2 in the human. With the exception of area 4, which showed inconsistent activation during punctate tactile stimulation, activation in these areas in the human consistently paralleled the pattern of activity observed in previous studies of monkey cortex.},
	language = {en},
	number = {1},
	urldate = {2020-03-16},
	journal = {Journal of Neurophysiology},
	author = {Moore, Christopher I. and Stern, Chantal E. and Corkin, Suzanne and Fischl, Bruce and Gray, Annette C. and Rosen, Bruce R. and Dale, Anders M.},
	month = jul,
	year = {2000},
	pages = {558--569}
}

The segregation of sensory information into distinct cortical areas is an important organizational feature of mammalian sensory systems. Here, we provide functional magnetic resonance imaging (fMRI) evidence for the functional delineation of somatosensory representations in the human central sulcus region. Data were collected with a 3-Tesla scanner during two stimulation protocols, a punctate tactile condition without a kinesthetic/motor component, and a kinesthetic/motor condition without a punctate tactile component. With three-dimensional (3-D) anatomical reconstruction techniques, we analyzed data in individual subjects, using the pattern of activation and the anatomical position of specific cortical areas to guide the analysis. As a complimentary analysis, we used a brain averaging technique that emphasized the similarity of cortical features in the morphing of individual subjects and thereby minimized the distortion of the location of cortical activation sites across individuals. A primary finding of this study was differential activation of the cortex on the fundus of the central sulcus, the position of area 3a, during the two tasks. Punctate tactile stimulation of the palm, administered at 3 Hz with a 5.88(log10.mg) von Frey filament, activated discrete regions within the precentral (PreCG) and postcentral (PoCG) gyri, corresponding to areas 6, 3b, 1, and 2, but did not activate area 3a. Conversely, kinesthetic/motor stimulation, 3-Hz flexion and extension of the digits, activated area 3a, the PreCG (areas 6 and 4), and the PoCG (areas 3b, 1, and 2). These activation patterns were observed in individual subjects and in the averaged data, providing strong evidence for the existence of a distinct representation within area 3a in humans. The percentage signal changes in the PreCG and PoCG regions activated by tactile stimulation, and in the intervening gap region, support this functional dissociation. In addition to this distinction within the fundus of the central sulcus, the combination of high-resolution imaging and 3-D analysis techniques permitted localization of activation within areas 6, 4, 3a, 3b, 1, and 2 in the human. With the exception of area 4, which showed inconsistent activation during punctate tactile stimulation, activation in these areas in the human consistently paralleled the pattern of activity observed in previous studies of monkey cortex.

@article{moore_referred_2000,
	title = {Referred phantom sensations and cortical reorganization after spinal cord injury in humans},
	volume = {97},
	issn = {0027-8424, 1091-6490},
	url = {http://www.pnas.org/cgi/doi/10.1073/pnas.250348997},
	doi = {10.1073/pnas.250348997},
	abstract = {To test the hypothesis that cortical remapping supports phantom sensations, we examined referred phantom sensations and cortical activation in humans after spinal-cord injury (SCI) at the thoracic level (T3-T12). Of 12 SCI subjects, 9 reported phantom sensations, and 2 reported referred phantom sensations. In both of these subjects, referred phantom sensations were evoked by contact in reference zones (RZ) that were not adjacent in the periphery and were not predicted to be adjacent in the postcentral gyrus (PoCG), suggesting that representations separated by centimeters of cortical space were simultaneously engaged. This finding was supported by functional MRI (fMRI). In a subject with a T6-level complete SCI, contact in RZ on the left or right forearm projected referred phantom sensations to the ipsilateral chest. During fMRI, contact in either forearm RZ evoked activity in the central PoCG (the position of the forearm representation) and the medial PoCG (the position of the chest representation) with {\textgreater}/=1.6 cm of nonresponsive cortex intervening. In contrast, stimulation in non-RZ forearm and palm regions in this subject and in lesion-matched SCI subjects evoked central but not medial PoCG activation. Our findings support a relation between PoCG activation and the percept of referred phantom sensations. These results, however, present an alternative to somatotopic cortical reorganization, namely, cortical plasticity expressed in coactivation of nonadjacent representations. The observed pattern suggests that somatotopic subcortical remapping, projected to the cortex, can support perceptual and cortical reorganization after deafferentation in humans.},
	language = {en},
	number = {26},
	urldate = {2020-03-16},
	journal = {Proceedings of the National Academy of Sciences},
	author = {Moore, C. I. and Stern, C. E. and Dunbar, C. and Kostyk, S. K. and Gehi, A. and Corkin, S.},
	month = dec,
	year = {2000},
	pages = {14703--14708},
	file = {Full Text:/Users/jjallen/Zotero/storage/2I6SP3ES/Moore et al. - 2000 - Referred phantom sensations and cortical reorganiz.pdf:application/pdf}
}

To test the hypothesis that cortical remapping supports phantom sensations, we examined referred phantom sensations and cortical activation in humans after spinal-cord injury (SCI) at the thoracic level (T3-T12). Of 12 SCI subjects, 9 reported phantom sensations, and 2 reported referred phantom sensations. In both of these subjects, referred phantom sensations were evoked by contact in reference zones (RZ) that were not adjacent in the periphery and were not predicted to be adjacent in the postcentral gyrus (PoCG), suggesting that representations separated by centimeters of cortical space were simultaneously engaged. This finding was supported by functional MRI (fMRI). In a subject with a T6-level complete SCI, contact in RZ on the left or right forearm projected referred phantom sensations to the ipsilateral chest. During fMRI, contact in either forearm RZ evoked activity in the central PoCG (the position of the forearm representation) and the medial PoCG (the position of the chest representation) with \textgreater/=1.6 cm of nonresponsive cortex intervening. In contrast, stimulation in non-RZ forearm and palm regions in this subject and in lesion-matched SCI subjects evoked central but not medial PoCG activation. Our findings support a relation between PoCG activation and the percept of referred phantom sensations. These results, however, present an alternative to somatotopic cortical reorganization, namely, cortical plasticity expressed in coactivation of nonadjacent representations. The observed pattern suggests that somatotopic subcortical remapping, projected to the cortex, can support perceptual and cortical reorganization after deafferentation in humans.

@article{hui_acupuncture_2000,
	title = {Acupuncture modulates the limbic system and subcortical gray structures of the human brain: evidence from {fMRI} studies in normal subjects},
	volume = {9},
	issn = {1065-9471},
	shorttitle = {Acupuncture modulates the limbic system and subcortical gray structures of the human brain},
	doi = {10.1002/(sici)1097-0193(2000)9:1<13::aid-hbm2>3.0.co;2-f},
	abstract = {Acupuncture, an ancient therapeutic technique, is emerging as an important modality of complementary medicine in the United States. The use and efficacy of acupuncture treatment are not yet widely accepted in Western scientific and medical communities. Demonstration of regionally specific, quantifiable acupuncture effects on relevant structures of the human brain would facilitate acceptance and integration of this therapeutic modality into the practice of modern medicine. Research with animal models of acupuncture indicates that many of the beneficial effects may be mediated at the subcortical level in the brain. We used functional magnetic resonance imaging (fMRI) to investigate the effects of acupuncture in normal subjects and to provide a foundation for future studies on mechanisms of acupuncture action in therapeutic interventions. Acupuncture needle manipulation was performed at Large Intestine 4 (LI 4, Hegu) on the hand in 13 subjects [Stux, 1997]. Needle manipulation on either hand produced prominent decreases of fMRI signals in the nucleus accumbens, amygdala, hippocampus, parahippocampus, hypothalamus, ventral tegmental area, anterior cingulate gyrus (BA 24), caudate, putamen, temporal pole, and insula in all 11 subjects who experienced acupuncture sensation. In marked contrast, signal increases were observed primarily in the somatosensory cortex. The two subjects who experienced pain instead of acupuncture sensation exhibited signal increases instead of decreases in the anterior cingulate gyrus (BA 24), caudate, putamen, anterior thalamus, and posterior insula. Superficial tactile stimulation to the same area elicited signal increases in the somatosensory cortex as expected, but no signal decreases in the deep structures. These preliminary results suggest that acupuncture needle manipulation modulates the activity of the limbic system and subcortical structures. We hypothesize that modulation of subcortical structures may be an important mechanism by which acupuncture exerts its complex multisystem effects.},
	language = {eng},
	number = {1},
	journal = {Human Brain Mapping},
	author = {Hui, K. K. and Liu, J. and Makris, N. and Gollub, R. L. and Chen, A. J. and Moore, C. I. and Kennedy, D. N. and Rosen, B. R. and Kwong, K. K.},
	year = {2000},
	pmid = {10643726},
	keywords = {Acupuncture Therapy, Adult, Female, Humans, Limbic System, Magnetic Resonance Imaging, Male, Middle Aged, Pain, Pain Measurement, Reference Values, Sensation, Somatosensory Cortex},
	pages = {13--25},
	file = {Submitted Version:/Users/jjallen/Zotero/storage/C4DFCJKA/Hui et al. - 2000 - Acupuncture modulates the limbic system and subcor.pdf:application/pdf}
}

Acupuncture, an ancient therapeutic technique, is emerging as an important modality of complementary medicine in the United States. The use and efficacy of acupuncture treatment are not yet widely accepted in Western scientific and medical communities. Demonstration of regionally specific, quantifiable acupuncture effects on relevant structures of the human brain would facilitate acceptance and integration of this therapeutic modality into the practice of modern medicine. Research with animal models of acupuncture indicates that many of the beneficial effects may be mediated at the subcortical level in the brain. We used functional magnetic resonance imaging (fMRI) to investigate the effects of acupuncture in normal subjects and to provide a foundation for future studies on mechanisms of acupuncture action in therapeutic interventions. Acupuncture needle manipulation was performed at Large Intestine 4 (LI 4, Hegu) on the hand in 13 subjects [Stux, 1997]. Needle manipulation on either hand produced prominent decreases of fMRI signals in the nucleus accumbens, amygdala, hippocampus, parahippocampus, hypothalamus, ventral tegmental area, anterior cingulate gyrus (BA 24), caudate, putamen, temporal pole, and insula in all 11 subjects who experienced acupuncture sensation. In marked contrast, signal increases were observed primarily in the somatosensory cortex. The two subjects who experienced pain instead of acupuncture sensation exhibited signal increases instead of decreases in the anterior cingulate gyrus (BA 24), caudate, putamen, anterior thalamus, and posterior insula. Superficial tactile stimulation to the same area elicited signal increases in the somatosensory cortex as expected, but no signal decreases in the deep structures. These preliminary results suggest that acupuncture needle manipulation modulates the activity of the limbic system and subcortical structures. We hypothesize that modulation of subcortical structures may be an important mechanism by which acupuncture exerts its complex multisystem effects.

@article{cramer_pilot_2000,
	title = {A {Pilot} {Study} of {Somatotopic} {Mapping} {After} {Cortical} {Infarct}},
	volume = {31},
	issn = {0039-2499, 1524-4628},
	url = {https://www.ahajournals.org/doi/10.1161/01.STR.31.3.668},
	doi = {10.1161/01.STR.31.3.668},
	abstract = {BACKGROUND AND PURPOSE:

Animal studies have described remodeling of sensory and motor representational maps after cortical infarct. These changes may contribute to return of function after stroke.
METHODS:

Functional MRI was used to compare sensory and motor maps obtained in 35 normal control subjects with results from 2 patients with good recovery 6 months after a cortical stroke.
RESULTS:

During finger tapping in controls, precentral gyrus activation exceeded or matched postcentral gyrus activation in 40 of 42 cases. Patient 1 had a small infarct limited to precentral gyrus. Finger tapping activated only postcentral gyrus, a pattern not seen in any control subject. During tactile stimulation of a finger or hand in controls, postcentral gyrus activation exceeded or matched precentral gyrus activation in 11 of 14 cases. Patient 2 had a small infarct limited to postcentral gyrus and superior parietal lobule. Tactile stimulation of the finger activated only precentral gyrus, a pattern not seen in any control. In both patients, activation during pectoralis contraction was medial to the site activated during finger tapping.
CONCLUSIONS:

Results during finger tapping (patient 1) and finger stimulation (patient 2) may reflect amplification of a preserved component of normal sensorimotor function, a shift in the cortical site of finger representation, or both. Cortical map reorganization along the infarct rim may be an important contributor to recovery of motor and sensory function after stroke. Functional MRI is useful for assessing motor and sensory representational maps.},
	language = {en},
	number = {3},
	urldate = {2020-03-16},
	journal = {Stroke},
	author = {Cramer, Steven C. and Moore, Christopher I. and Finklestein, Seth P. and Rosen, Bruce R.},
	month = mar,
	year = {2000},
	pages = {668--671},
	file = {Full Text:/Users/jjallen/Zotero/storage/NAQIBKVH/Cramer et al. - 2000 - A Pilot Study of Somatotopic Mapping After Cortica.pdf:application/pdf}
}

BACKGROUND AND PURPOSE: Animal studies have described remodeling of sensory and motor representational maps after cortical infarct. These changes may contribute to return of function after stroke. METHODS: Functional MRI was used to compare sensory and motor maps obtained in 35 normal control subjects with results from 2 patients with good recovery 6 months after a cortical stroke. RESULTS: During finger tapping in controls, precentral gyrus activation exceeded or matched postcentral gyrus activation in 40 of 42 cases. Patient 1 had a small infarct limited to precentral gyrus. Finger tapping activated only postcentral gyrus, a pattern not seen in any control subject. During tactile stimulation of a finger or hand in controls, postcentral gyrus activation exceeded or matched precentral gyrus activation in 11 of 14 cases. Patient 2 had a small infarct limited to postcentral gyrus and superior parietal lobule. Tactile stimulation of the finger activated only precentral gyrus, a pattern not seen in any control. In both patients, activation during pectoralis contraction was medial to the site activated during finger tapping. CONCLUSIONS: Results during finger tapping (patient 1) and finger stimulation (patient 2) may reflect amplification of a preserved component of normal sensorimotor function, a shift in the cortical site of finger representation, or both. Cortical map reorganization along the infarct rim may be an important contributor to recovery of motor and sensory function after stroke. Functional MRI is useful for assessing motor and sensory representational maps.

@article{moore_dynamics_1999,
	title = {Dynamics of neuronal processing in rat somatosensory cortex},
	volume = {22},
	issn = {01662236},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0166223699014526},
	doi = {10.1016/S0166-2236(99)01452-6},
	abstract = {Recently, the study of sensory cortex has focused on the context-dependent evolution of receptive fields and cortical maps over millisecond to second time-scales. This article reviews advances in our understanding of these processes in the rat primary somatosensory cortex (SI). Subthreshold input to individual rat SI neurons is extensive, spanning several vibrissae from the center of the receptive field, and arrives within 25 ms of vibrissa deflection. These large subthreshold receptive fields provide a broad substrate for rapid excitatory and inhibitory multi-vibrissa interactions. The 'whisking' behavior, an approximately 8 Hz ellipsoid movement of the vibrissae, introduces a context-dependent change in the pattern of vibrissa movement during tactile exploration. Stimulation of vibrissae over this frequency range modulates the pattern of activity in thalamic and cortical neurons, and, at the level of the cortical map, focuses the extent of the vibrissa representation relative to lower frequency stimulation (1 Hz). These findings suggest that one function of whisking is to reset cortical organization to improve tactile discrimination. Recent discoveries in primary visual cortex (VI) demonstrate parallel non-linearities in center-surround interactions in rat SI and VI, and provide a model for the rapid integration of multi-vibrissa input. The studies discussed in this article suggest that, despite its original conception as a uniquely segregated cortex, rat SI has a wide array of dynamic interactions, and that the study of this region will provide insight into the general mechanisms of cortical dynamics engaged by sensory systems.},
	language = {en},
	number = {11},
	urldate = {2020-03-10},
	journal = {Trends in Neurosciences},
	author = {Moore, Christopher I. and Nelson, Sacha B. and Sur, Mriganka},
	month = nov,
	year = {1999},
	pages = {513--520}
}

Recently, the study of sensory cortex has focused on the context-dependent evolution of receptive fields and cortical maps over millisecond to second time-scales. This article reviews advances in our understanding of these processes in the rat primary somatosensory cortex (SI). Subthreshold input to individual rat SI neurons is extensive, spanning several vibrissae from the center of the receptive field, and arrives within 25 ms of vibrissa deflection. These large subthreshold receptive fields provide a broad substrate for rapid excitatory and inhibitory multi-vibrissa interactions. The 'whisking' behavior, an approximately 8 Hz ellipsoid movement of the vibrissae, introduces a context-dependent change in the pattern of vibrissa movement during tactile exploration. Stimulation of vibrissae over this frequency range modulates the pattern of activity in thalamic and cortical neurons, and, at the level of the cortical map, focuses the extent of the vibrissa representation relative to lower frequency stimulation (1 Hz). These findings suggest that one function of whisking is to reset cortical organization to improve tactile discrimination. Recent discoveries in primary visual cortex (VI) demonstrate parallel non-linearities in center-surround interactions in rat SI and VI, and provide a model for the rapid integration of multi-vibrissa input. The studies discussed in this article suggest that, despite its original conception as a uniquely segregated cortex, rat SI has a wide array of dynamic interactions, and that the study of this region will provide insight into the general mechanisms of cortical dynamics engaged by sensory systems.

@article{sheth_temporal_1998,
	title = {Temporal {Modulation} of {Spatial} {Borders} in {Rat} {Barrel} {Cortex}},
	volume = {79},
	issn = {0022-3077, 1522-1598},
	url = {https://www.physiology.org/doi/10.1152/jn.1998.79.1.464},
	doi = {10.1152/jn.1998.79.1.464},
	abstract = {We examined the effects of varying vibrissa stimulation frequency on intrinsic signal and neuronal responses in rat barrel cortex. Optical imaging of intrinsic signals demonstrated that the region of cortex activated by deflection of a single vibrissa at 1 Hz is more diffuse and more widespread than the territory activated at 5 or 10 Hz. With the use of two different paradigms, constant time of stimulation and constant number of vibrissa deflections, we showed that the optically imaged spread of activity is more discrete at higher stimulation frequencies. We combined optical imaging with multiple electrode recording and confirmed that the neuronal response to individual vibrissa stimulation at the optically imaged center of activity is greater than the response away from the imaged center. Consistent with the imaging data, these recordings also showed no response to a second vibrissa deflection at 5 Hz at a peripheral recording site, though there was a significant response to a second vibrissa deflection at 1 Hz at the same peripheral site. These findings demonstrate that vibrissa stimulation at higher frequencies leads to more focused physiological responses in cortex. Thus the spread of activation in rat barrel cortex is modulated in a dynamic fashion by the frequency of vibrissa stimulation.},
	language = {en},
	number = {1},
	urldate = {2020-03-10},
	journal = {Journal of Neurophysiology},
	author = {Sheth, Bhavin R. and Moore, Christopher I. and Sur, Mriganka},
	month = jan,
	year = {1998},
	pages = {464--470},
	file = {Submitted Version:/Users/jjallen/Zotero/storage/TLY9WJXP/Sheth et al. - 1998 - Temporal Modulation of Spatial Borders in Rat Barr.pdf:application/pdf}
}

We examined the effects of varying vibrissa stimulation frequency on intrinsic signal and neuronal responses in rat barrel cortex. Optical imaging of intrinsic signals demonstrated that the region of cortex activated by deflection of a single vibrissa at 1 Hz is more diffuse and more widespread than the territory activated at 5 or 10 Hz. With the use of two different paradigms, constant time of stimulation and constant number of vibrissa deflections, we showed that the optically imaged spread of activity is more discrete at higher stimulation frequencies. We combined optical imaging with multiple electrode recording and confirmed that the neuronal response to individual vibrissa stimulation at the optically imaged center of activity is greater than the response away from the imaged center. Consistent with the imaging data, these recordings also showed no response to a second vibrissa deflection at 5 Hz at a peripheral recording site, though there was a significant response to a second vibrissa deflection at 1 Hz at the same peripheral site. These findings demonstrate that vibrissa stimulation at higher frequencies leads to more focused physiological responses in cortex. Thus the spread of activation in rat barrel cortex is modulated in a dynamic fashion by the frequency of vibrissa stimulation.

@article{moore_spatio-temporal_1998,
	title = {Spatio-{Temporal} {Subthreshold} {Receptive} {Fields} in the {Vibrissa} {Representation} of {Rat} {Primary} {Somatosensory} {Cortex}},
	volume = {80},
	issn = {0022-3077, 1522-1598},
	url = {https://www.physiology.org/doi/10.1152/jn.1998.80.6.2882},
	doi = {10.1152/jn.1998.80.6.2882},
	abstract = {Spatio-temporal subthreshold receptive fields in the vibrissa representation of rat primary somatosensory cortex. J. Neurophysiol. 80: 2882–2892, 1998. Whole cell recordings of synaptic responses evoked by deflection of individual vibrissa were obtained from neurons within adult rat primary somatosensory cortex. To define the spatial and temporal properties of subthreshold receptive fields, the spread, amplitude, latency to onset, rise time to half peak amplitude, and the balance of excitation and inhibition of subthreshold input were quantified. The convergence of information onto single neurons was found to be extensive: inputs were consistently evoked by vibrissa one- and two-away from the vibrissa that evoked the largest response (the “primary vibrissa”). Latency to onset, rise time, and the incidence and strength of inhibitory postsynaptic potentials (IPSPs) varied as a function of position within the receptive field and the strength of evoked excitatory input. Nonprimary vibrissae evoked smaller amplitude subthreshold responses [primary vibrissa, 9.1 ± 0.84 (SE) mV, n = 14; 1-away, 5.1 ± 0.5 mV, n = 38; 2-away, 3.7 ± 0.59 mV, n = 22; 3-away, 1.3 ± 0.70 mV, n = 8] with longer latencies (primary vibrissa, 10.8 ± 0.80 ms; 1-away, 15.0 ± 1.2 ms; 2-away, 15.7 ± 2.0 ms). Rise times were significantly faster for inputs that could evoke action potential responses (suprathreshold, 4.1 ± 1.3 ms, n = 8; subthreshold, 12.4 ± 1.5 ms, n = 61). In a subset of cells, sensory evoked IPSPs were examined by deflecting vibrissa during injection of hyperpolarizing and depolarizing current. The strongest IPSPs were evoked by the primary vibrissa ( n = 5/5), but smaller IPSPs also were evoked by nonprimary vibrissae ( n = 8/13). Inhibition peaked by 10–20 ms after the onset of the fastest excitatory input to the cortex. This pattern of inhibitory activity led to a functional reversal of the center of the receptive field and to suppression of later-arriving and slower-rising nonprimary inputs. Together, these data demonstrate that subthreshold receptive fields are on average large, and the spatio-temporal dynamics of these receptive fields vary as a function of position within the receptive field and strength of excitatory input. These findings constrain models of suprathreshold receptive field generation, multivibrissa interactions, and cortical plasticity.},
	language = {en},
	number = {6},
	urldate = {2020-03-10},
	journal = {Journal of Neurophysiology},
	author = {Moore, Christopher I. and Nelson, Sacha B.},
	month = dec,
	year = {1998},
	pages = {2882--2892},
	file = {Submitted Version:/Users/jjallen/Zotero/storage/5FGQR992/Moore and Nelson - 1998 - Spatio-Temporal Subthreshold Receptive Fields in t.pdf:application/pdf}
}

Spatio-temporal subthreshold receptive fields in the vibrissa representation of rat primary somatosensory cortex. J. Neurophysiol. 80: 2882–2892, 1998. Whole cell recordings of synaptic responses evoked by deflection of individual vibrissa were obtained from neurons within adult rat primary somatosensory cortex. To define the spatial and temporal properties of subthreshold receptive fields, the spread, amplitude, latency to onset, rise time to half peak amplitude, and the balance of excitation and inhibition of subthreshold input were quantified. The convergence of information onto single neurons was found to be extensive: inputs were consistently evoked by vibrissa one- and two-away from the vibrissa that evoked the largest response (the “primary vibrissa”). Latency to onset, rise time, and the incidence and strength of inhibitory postsynaptic potentials (IPSPs) varied as a function of position within the receptive field and the strength of evoked excitatory input. Nonprimary vibrissae evoked smaller amplitude subthreshold responses [primary vibrissa, 9.1 ± 0.84 (SE) mV, n = 14; 1-away, 5.1 ± 0.5 mV, n = 38; 2-away, 3.7 ± 0.59 mV, n = 22; 3-away, 1.3 ± 0.70 mV, n = 8] with longer latencies (primary vibrissa, 10.8 ± 0.80 ms; 1-away, 15.0 ± 1.2 ms; 2-away, 15.7 ± 2.0 ms). Rise times were significantly faster for inputs that could evoke action potential responses (suprathreshold, 4.1 ± 1.3 ms, n = 8; subthreshold, 12.4 ± 1.5 ms, n = 61). In a subset of cells, sensory evoked IPSPs were examined by deflecting vibrissa during injection of hyperpolarizing and depolarizing current. The strongest IPSPs were evoked by the primary vibrissa ( n = 5/5), but smaller IPSPs also were evoked by nonprimary vibrissae ( n = 8/13). Inhibition peaked by 10–20 ms after the onset of the fastest excitatory input to the cortex. This pattern of inhibitory activity led to a functional reversal of the center of the receptive field and to suppression of later-arriving and slower-rising nonprimary inputs. Together, these data demonstrate that subthreshold receptive fields are on average large, and the spatio-temporal dynamics of these receptive fields vary as a function of position within the receptive field and strength of excitatory input. These findings constrain models of suprathreshold receptive field generation, multivibrissa interactions, and cortical plasticity.

@article{locascio_time_1997,
	title = {Time series analysis in the time domain and resampling methods for studies of functional magnetic resonance brain imaging},
	volume = {5},
	issn = {1065-9471},
	doi = {10.1002/(SICI)1097-0193(1997)5:3<168::AID-HBM3>3.0.CO;2-1},
	abstract = {Although functional magnetic resonance imaging (fMRI) methods yield rich temporal and spatial data for even a single subject, universally accepted data analysis techniques have not been developed that use all the potential information from fMRI of the brain. Specifically, temporal correlations and confounds are a problem in assessing change within pixels. Spatial correlations across pixels are a problem in determining regions of activation and in correcting for multiple significance tests. We propose methods that address these issues in the analysis of task-related changes in mean signal intensity for individual subjects. Our approach to temporally based problems within pixels is to employ a model based on autoregressive-moving average (ARMA or "Box-Jenkins") time series methods, which we call CARMA (Contrasts and ARMA). To adjust for performing multiple significance tests across pixels, taking into account between-pixel correlations, we propose adjustment of P values with "resampling methods." Our objective is to produce two- or three-dimensional brain maps that provide, at each pixel in the map, an estimated P value with absolute meaning. That is, each P value approximates the probability of having obtained by chance the observed signal effect at that pixel, given that the null hypothesis is true. Simulated and real data examples are provided.},
	language = {eng},
	number = {3},
	journal = {Human Brain Mapping},
	author = {Locascio, J. J. and Jennings, P. J. and Moore, C. I. and Corkin, S.},
	year = {1997},
	pmid = {20408214},
	pages = {168--193},
	file = {Submitted Version:/Users/jjallen/Zotero/storage/CIMI3DLX/Locascio et al. - 1997 - Time series analysis in the time domain and resamp.pdf:application/pdf}
}

Although functional magnetic resonance imaging (fMRI) methods yield rich temporal and spatial data for even a single subject, universally accepted data analysis techniques have not been developed that use all the potential information from fMRI of the brain. Specifically, temporal correlations and confounds are a problem in assessing change within pixels. Spatial correlations across pixels are a problem in determining regions of activation and in correcting for multiple significance tests. We propose methods that address these issues in the analysis of task-related changes in mean signal intensity for individual subjects. Our approach to temporally based problems within pixels is to employ a model based on autoregressive-moving average (ARMA or "Box-Jenkins") time series methods, which we call CARMA (Contrasts and ARMA). To adjust for performing multiple significance tests across pixels, taking into account between-pixel correlations, we propose adjustment of P values with "resampling methods." Our objective is to produce two- or three-dimensional brain maps that provide, at each pixel in the map, an estimated P value with absolute meaning. That is, each P value approximates the probability of having obtained by chance the observed signal effect at that pixel, given that the null hypothesis is true. Simulated and real data examples are provided.

@article{nayak_ca2calmodulin-dependent_1996,
	title = {Ca2+/calmodulin-dependent protein kinase {II} phosphorylation of the presynaptic protein synapsin {I} is persistently increased during long-term potentiation},
	volume = {93},
	issn = {0027-8424, 1091-6490},
	url = {http://www.pnas.org/cgi/doi/10.1073/pnas.93.26.15451},
	doi = {10.1073/pnas.93.26.15451},
	abstract = {Long-term potentiation (LTP) is an increase in synaptic responsiveness thought to be involved in mammalian learning and memory. The localization (presynaptic and/or postsynaptic) of changes underlying LTP has been difficult to resolve with current electrophysiological techniques. Using a biochemical approach, we have addressed this issue and attempted to identify specific molecular mechanisms that may underlie LTP. We utilized a novel multiple-electrode stimulator to produce LTP in a substantial portion of the synapses in a hippocampal CA1 minislice and tested the effects of such stimulation on the presynaptic protein synapsin I. LTP-inducing stimulation produced a long-lasting 6-fold increase in the phosphorylation of synapsin I at its Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) sites without affecting synapsin I levels. This effect was fully blocked by either the N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (APV) or the CaM kinase II inhibitor KN-62. Our results indicate that LTP expression is accompanied by persistent changes in presynaptic phosphorylation, and specifically that presynaptic CaM kinase II activity and synapsin I phosphorylation may be involved in LTP expression.},
	language = {en},
	number = {26},
	urldate = {2020-03-10},
	journal = {Proceedings of the National Academy of Sciences},
	author = {Nayak, A. S. and Moore, C. I. and Browning, M. D.},
	month = dec,
	year = {1996},
	pages = {15451--15456},
	file = {Full Text:/Users/jjallen/Zotero/storage/LTUCSE72/Nayak et al. - 1996 - Ca2+calmodulin-dependent protein kinase II phosph.pdf:application/pdf}
}

Long-term potentiation (LTP) is an increase in synaptic responsiveness thought to be involved in mammalian learning and memory. The localization (presynaptic and/or postsynaptic) of changes underlying LTP has been difficult to resolve with current electrophysiological techniques. Using a biochemical approach, we have addressed this issue and attempted to identify specific molecular mechanisms that may underlie LTP. We utilized a novel multiple-electrode stimulator to produce LTP in a substantial portion of the synapses in a hippocampal CA1 minislice and tested the effects of such stimulation on the presynaptic protein synapsin I. LTP-inducing stimulation produced a long-lasting 6-fold increase in the phosphorylation of synapsin I at its Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) sites without affecting synapsin I levels. This effect was fully blocked by either the N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (APV) or the CaM kinase II inhibitor KN-62. Our results indicate that LTP expression is accompanied by persistent changes in presynaptic phosphorylation, and specifically that presynaptic CaM kinase II activity and synapsin I phosphorylation may be involved in LTP expression.

@article{cramer_transient_1995,
	title = {Transient expression of {NADPH}-diaphorase in the lateral geniculate nucleus of the ferret during early postnatal development},
	volume = {353},
	issn = {0021-9967, 1096-9861},
	url = {http://doi.wiley.com/10.1002/cne.903530211},
	doi = {10.1002/cne.903530211},
	abstract = {Retinogeniculate projections in the ferret are refined during postnatal development so that inputs from the two eyes become segregated into eye-specific laminae, and each eye-specific lamina is further divided into sublaminae containing inputs from on-center or off-center afferents. Segregation into eye-specific laminae and on/off sublaminae is dependent on neuronal activity; sublamination depends on activation of N-methyl-d-aspartate (NMDA) receptors. By analogy with the suggested role of nitric oxide in NMDA-mediated long-term potentiation in the hippocampus, we investigated a possible role for nitric oxide in ferret retinogeniculate development. The expression of NADPH-diaphorase, a nitric oxide synthase, was examined histologically in the lateral geniculate nucleus of ferrets at several postnatal ages. At birth, neuropil is labeled in the nucleus, although no cell bodies are visible. After the first postnatal week, some labeled cells appear, predominantly in the C laminae. By three postnatal weeks, cell bodies are clearly labeled in all geniculate laminae. Staining reaches a peak in density at about four postnatal weeks, then declines such that by six postnatal weeks labeled cells are no longer visible. This transient expression of NADPH-diaphorase activity is consistent with a role for nitric oxide in the development of mature connections within the ferret lateral geniculate nucleus.},
	language = {en},
	number = {2},
	urldate = {2020-03-10},
	journal = {The Journal of Comparative Neurology},
	author = {Cramer, Karina S. and Moore, Christopher I. and Sur, Mriganka},
	month = mar,
	year = {1995},
	pages = {306--316}
}

Retinogeniculate projections in the ferret are refined during postnatal development so that inputs from the two eyes become segregated into eye-specific laminae, and each eye-specific lamina is further divided into sublaminae containing inputs from on-center or off-center afferents. Segregation into eye-specific laminae and on/off sublaminae is dependent on neuronal activity; sublamination depends on activation of N-methyl-d-aspartate (NMDA) receptors. By analogy with the suggested role of nitric oxide in NMDA-mediated long-term potentiation in the hippocampus, we investigated a possible role for nitric oxide in ferret retinogeniculate development. The expression of NADPH-diaphorase, a nitric oxide synthase, was examined histologically in the lateral geniculate nucleus of ferrets at several postnatal ages. At birth, neuropil is labeled in the nucleus, although no cell bodies are visible. After the first postnatal week, some labeled cells appear, predominantly in the C laminae. By three postnatal weeks, cell bodies are clearly labeled in all geniculate laminae. Staining reaches a peak in density at about four postnatal weeks, then declines such that by six postnatal weeks labeled cells are no longer visible. This transient expression of NADPH-diaphorase activity is consistent with a role for nitric oxide in the development of mature connections within the ferret lateral geniculate nucleus.

@article{moore_hippocampal_1993,
	title = {Hippocampal plasticity induced by primed burst, but not long-term potentiation, stimulation is impaired in area {CA1} of aged fischer 344 rats},
	volume = {3},
	issn = {1050-9631, 1098-1063},
	url = {http://doi.wiley.com/10.1002/hipo.450030106},
	doi = {10.1002/hipo.450030106},
	abstract = {The effect of two types of electrical stimulation designed to induce long-lasting plasticity of the Schaffer/commissural inputs to CA1 pyramidal neurons was investigated using in vitro hippocampal slices made from young (3-6 month) and old (24-27 month) Fischer 344 rats. The first stimulation paradigm, primed burst (PB) stimulation, consisted of a total of five physiologically patterned stimuli: a single priming pulse followed 170 ms later by a burst of four pulses at 200 Hz. The second stimulation paradigm, long-term potentiation (LTP) stimulation, consisted of a 200 Hz/1 second train (a total of 200 stimuli). Primed burst and LTP stimulation were equally effective at inducing a lasting increase in the population spike recorded from slices made from young rats. However, the enhancement of population spike amplitude produced by PB, but not LTP, stimulation was significantly less in slices made from old rats. These results suggest that the capacity of the hippocampus to demonstrate long-lasting synaptic plasticity is not altered with age, but that engaging plasticity-inducing mechanisms becomes more difficult. Furthermore, these data suggest that physiologically patterned paradigms for inducing long-lasting synaptic plasticity may more accurately assess the functional status of hippocampal memory encoding mechanisms than does conventional LTP stimulation.},
	language = {en},
	number = {1},
	urldate = {2020-03-16},
	journal = {Hippocampus},
	author = {Moore, Christopher I. and Browning, Michael D. and Rose, Gregory M.},
	month = jan,
	year = {1993},
	pages = {57--66}
}

%%% ====================================================================
%%% Acknowledgement abbreviations:

The effect of two types of electrical stimulation designed to induce long-lasting plasticity of the Schaffer/commissural inputs to CA1 pyramidal neurons was investigated using in vitro hippocampal slices made from young (3-6 month) and old (24-27 month) Fischer 344 rats. The first stimulation paradigm, primed burst (PB) stimulation, consisted of a total of five physiologically patterned stimuli: a single priming pulse followed 170 ms later by a burst of four pulses at 200 Hz. The second stimulation paradigm, long-term potentiation (LTP) stimulation, consisted of a 200 Hz/1 second train (a total of 200 stimuli). Primed burst and LTP stimulation were equally effective at inducing a lasting increase in the population spike recorded from slices made from young rats. However, the enhancement of population spike amplitude produced by PB, but not LTP, stimulation was significantly less in slices made from old rats. These results suggest that the capacity of the hippocampus to demonstrate long-lasting synaptic plasticity is not altered with age, but that engaging plasticity-inducing mechanisms becomes more difficult. Furthermore, these data suggest that physiologically patterned paradigms for inducing long-lasting synaptic plasticity may more accurately assess the functional status of hippocampal memory encoding mechanisms than does conventional LTP stimulation.