Efficient opto- and chemogenetic control in a single molecule driven by FRET-modified bioluminescence. Björefeldt, A., Murphy, J., Crespo, E. L., Lambert, G. G., Prakash, M., Ikefuama, E. C., Friedman, N., Brown, T. M., Lipscombe, D., Moore, C. I., Hochgeschwender, U., & Shaner, N. C. Neurophotonics, 11(2):021005, April, 2024. Place: United Statesdoi abstract bibtex 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.
@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},
}
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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":[{"propositions":[],"lastnames":["Björefeldt"],"firstnames":["Andreas"],"suffixes":[]},{"propositions":[],"lastnames":["Murphy"],"firstnames":["Jeremy"],"suffixes":[]},{"propositions":[],"lastnames":["Crespo"],"firstnames":["Emmanuel","L."],"suffixes":[]},{"propositions":[],"lastnames":["Lambert"],"firstnames":["Gerard","G."],"suffixes":[]},{"propositions":[],"lastnames":["Prakash"],"firstnames":["Mansi"],"suffixes":[]},{"propositions":[],"lastnames":["Ikefuama"],"firstnames":["Ebenezer","C."],"suffixes":[]},{"propositions":[],"lastnames":["Friedman"],"firstnames":["Nina"],"suffixes":[]},{"propositions":[],"lastnames":["Brown"],"firstnames":["Tariq","M."],"suffixes":[]},{"propositions":[],"lastnames":["Lipscombe"],"firstnames":["Diane"],"suffixes":[]},{"propositions":[],"lastnames":["Moore"],"firstnames":["Christopher","I."],"suffixes":[]},{"propositions":[],"lastnames":["Hochgeschwender"],"firstnames":["Ute"],"suffixes":[]},{"propositions":[],"lastnames":["Shaner"],"firstnames":["Nathan","C."],"suffixes":[]}],"month":"April","year":"2024","pmid":"38450294","pmcid":"PMC10917299","note":"Place: United States","keywords":"bioluminescence, Bioluminescent optogenetics, chemogenetics, luminopsin, optogenetics","pages":"021005","bibtex":"@article{bjorefeldt_efficient_2024,\n\ttitle = {Efficient opto- and chemogenetic control in a single molecule driven by {FRET}-modified bioluminescence.},\n\tvolume = {11},\n\tcopyright = {© 2024 The Authors.},\n\tissn = {2329-423X 2329-4248},\n\tdoi = {10.1117/1.NPh.11.2.021005},\n\tabstract = {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.},\n\tlanguage = {eng},\n\tnumber = {2},\n\tjournal = {Neurophotonics},\n\tauthor = {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.},\n\tmonth = apr,\n\tyear = {2024},\n\tpmid = {38450294},\n\tpmcid = {PMC10917299},\n\tnote = {Place: United States},\n\tkeywords = {bioluminescence, Bioluminescent optogenetics, chemogenetics, luminopsin, optogenetics},\n\tpages = {021005},\n}\n\n","author_short":["Björefeldt, A.","Murphy, J.","Crespo, E. L.","Lambert, G. G.","Prakash, M.","Ikefuama, E. C.","Friedman, N.","Brown, T. M.","Lipscombe, D.","Moore, C. I.","Hochgeschwender, U.","Shaner, N. 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