@article{
 title = {Attractor-like circuits improve visual decoding and behavior in zebrafish},
 type = {article},
 year = {2024},
 pages = {2024.02.03.578596},
 websites = {https://www.biorxiv.org/content/10.1101/2024.02.03.578596v1},
 month = {2},
 publisher = {Cold Spring Harbor Laboratory},
 day = {4},
 id = {b7f52441-6ae7-355c-99c7-e7907d000e24},
 created = {2024-02-21T14:11:39.611Z},
 accessed = {2024-02-21},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2024-02-21T14:17:25.730Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Attractor networks are neural circuits with stable states that represent information or memories. They play a crucial role in memory retrieval, decision-making and integrating noisy cues. In zebrafish larvae, the spontaneous dynamics of the optic tectum is structured according to topographically organized neuronal assemblies exhibiting attractor-like behavior. Here, we took advantage of the Methyl-CpG-binding protein 2 (MeCP2) deficient zebrafish mutant, which displays perturbed tectal dynamics, to study the functional role of the attractor-like circuits in visual processing. In comparison to wild-type larvae, the mecp2 -mutant showed reduced functional connectivity in the optic tectum. This abnormal connectivity significantly affected the visual response, and the ability to discriminate between visual stimuli. Finally, the mutant larvae where less efficient in hunting paramecia. We argue that the attractor dynamics of the tectal assemblies improve stimulus discrimination, visual resolution, and increase the sensitivity to behaviorally relevant visual stimuli. ### Competing Interest Statement The authors have declared no competing interest.},
 bibtype = {article},
 author = {Privat, Martin and Hansen, Enrique Carlos Arnoldo and Pietri, Thomas and Marachlian, Emiliano and Uribe-Arias, Alejandro and Duchemin, Auriane and Candat, Virginie and Nourin, Sarah and Sumbre, Germán},
 doi = {10.1101/2024.02.03.578596},
 journal = {bioRxiv}
}

Attractor networks are neural circuits with stable states that represent information or memories. They play a crucial role in memory retrieval, decision-making and integrating noisy cues. In zebrafish larvae, the spontaneous dynamics of the optic tectum is structured according to topographically organized neuronal assemblies exhibiting attractor-like behavior. Here, we took advantage of the Methyl-CpG-binding protein 2 (MeCP2) deficient zebrafish mutant, which displays perturbed tectal dynamics, to study the functional role of the attractor-like circuits in visual processing. In comparison to wild-type larvae, the mecp2 -mutant showed reduced functional connectivity in the optic tectum. This abnormal connectivity significantly affected the visual response, and the ability to discriminate between visual stimuli. Finally, the mutant larvae where less efficient in hunting paramecia. We argue that the attractor dynamics of the tectal assemblies improve stimulus discrimination, visual resolution, and increase the sensitivity to behaviorally relevant visual stimuli. ### Competing Interest Statement The authors have declared no competing interest.

@article{
 title = {Radial astrocyte synchronization modulates the visual system during behavioral-state transitions},
 type = {article},
 year = {2023},
 pages = {4040-4057.e6},
 volume = {111},
 websites = {https://linkinghub.elsevier.com/retrieve/pii/S0896627323007092},
 month = {12},
 id = {024fc6ef-70e4-33e4-8fec-1335f6050d55},
 created = {2023-10-19T23:54:43.540Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2023-12-21T23:36:19.241Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Uribe-Arias, Alejandro and Rozenblat, Rotem and Vinepinsky, Ehud and Marachlian, Emiliano and Kulkarni, Anirudh and Zada, David and Privat, Martin and Topsakalian, Diego and Charpy, Sarah and Candat, Virginie and Nourin, Sarah and Appelbaum, Lior and Sumbre, Germán},
 doi = {10.1016/j.neuron.2023.09.022},
 journal = {Neuron},
 number = {24}
}

@article{
 title = {Blind cavefish retain functional connectivity in the tectum despite loss of retinal input},
 type = {article},
 year = {2022},
 keywords = {cavefish,neural circuit evolution,visual processing},
 pages = {2021.09.28.461408},
 volume = {32},
 websites = {https://linkinghub.elsevier.com/retrieve/pii/S0960982222011162},
 month = {9},
 publisher = {Cold Spring Harbor Laboratory},
 day = {29},
 id = {1280bc16-25e4-3990-ac3a-4f8e67b26a94},
 created = {2022-10-13T10:15:15.103Z},
 accessed = {2021-10-06},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2024-02-21T14:06:02.133Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Sensory systems display remarkable plasticity and are under strong evolutionary selection. The Mexican cavefish, Astyanax mexicanus , consists of eyed river-dwelling surface populations, and multiple independent cave populations which have converged on eye loss, providing the opportunity to examine the evolution of sensory circuits in response to environmental perturbation. Functional analysis across multiple transgenic populations expressing GCaMP6s showed that functional connectivity of the optic tectum largely did not differ between populations, except for the selective loss of negatively correlated activity within the cavefish tectum, suggesting positively correlated neural activity is resistant to an evolved loss of input from the retina. Further, analysis of surface-cave hybrid fish reveals that changes in the tectum are genetically distinct from those encoding eye-loss. Together, these findings uncover the independent evolution of multiple components of the visual system and establish the use of functional imaging in A. mexicanus to study neural circuit evolution. ### Competing Interest Statement The authors have declared no competing interest.},
 bibtype = {article},
 author = {Lloyd, Evan and McDole, Brittnee and Privat, Martin and Jaggard, James B. and Duboué, Erik R. and Sumbre, Germán German and Keene, Alex C.},
 doi = {10.1016/j.cub.2022.07.015},
 journal = {Current Biology},
 number = {17}
}

Sensory systems display remarkable plasticity and are under strong evolutionary selection. The Mexican cavefish, Astyanax mexicanus , consists of eyed river-dwelling surface populations, and multiple independent cave populations which have converged on eye loss, providing the opportunity to examine the evolution of sensory circuits in response to environmental perturbation. Functional analysis across multiple transgenic populations expressing GCaMP6s showed that functional connectivity of the optic tectum largely did not differ between populations, except for the selective loss of negatively correlated activity within the cavefish tectum, suggesting positively correlated neural activity is resistant to an evolved loss of input from the retina. Further, analysis of surface-cave hybrid fish reveals that changes in the tectum are genetically distinct from those encoding eye-loss. Together, these findings uncover the independent evolution of multiple components of the visual system and establish the use of functional imaging in A. mexicanus to study neural circuit evolution. ### Competing Interest Statement The authors have declared no competing interest.

@article{
 title = {Blind cavefish retain functional connectivity in the tectum despite loss of retinal input},
 type = {article},
 year = {2021},
 pages = {2021.09.28.461408},
 websites = {https://www.biorxiv.org/content/10.1101/2021.09.28.461408v1},
 month = {9},
 publisher = {Cold Spring Harbor Laboratory},
 day = {29},
 id = {f5983e94-2a5f-3169-83b9-457d5222465b},
 created = {2021-10-06T11:42:49.431Z},
 accessed = {2021-10-06},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2023-05-03T19:59:38.515Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Sensory systems display remarkable plasticity and are under strong evolutionary selection. The Mexican cavefish, Astyanax mexicanus , consists of eyed river-dwelling surface populations, and multiple independent cave populations which have converged on eye loss, providing the opportunity to examine the evolution of sensory circuits in response to environmental perturbation. Functional analysis across multiple transgenic populations expressing GCaMP6s showed that functional connectivity of the optic tectum largely did not differ between populations, except for the selective loss of negatively correlated activity within the cavefish tectum, suggesting positively correlated neural activity is resistant to an evolved loss of input from the retina. Further, analysis of surface-cave hybrid fish reveals that changes in the tectum are genetically distinct from those encoding eye-loss. Together, these findings uncover the independent evolution of multiple components of the visual system and establish the use of functional imaging in A. mexicanus to study neural circuit evolution. ### Competing Interest Statement The authors have declared no competing interest.},
 bibtype = {article},
 author = {Lloyd, Evan and McDole, Brittnee and Privat, Martin and Jaggard, James B. and Duboué, Erik and Sumbre, Germán and Keene, Alex},
 doi = {10.1101/2021.09.28.461408},
 journal = {bioRxiv}
}

Sensory systems display remarkable plasticity and are under strong evolutionary selection. The Mexican cavefish, Astyanax mexicanus , consists of eyed river-dwelling surface populations, and multiple independent cave populations which have converged on eye loss, providing the opportunity to examine the evolution of sensory circuits in response to environmental perturbation. Functional analysis across multiple transgenic populations expressing GCaMP6s showed that functional connectivity of the optic tectum largely did not differ between populations, except for the selective loss of negatively correlated activity within the cavefish tectum, suggesting positively correlated neural activity is resistant to an evolved loss of input from the retina. Further, analysis of surface-cave hybrid fish reveals that changes in the tectum are genetically distinct from those encoding eye-loss. Together, these findings uncover the independent evolution of multiple components of the visual system and establish the use of functional imaging in A. mexicanus to study neural circuit evolution. ### Competing Interest Statement The authors have declared no competing interest.

@article{
 title = {Fourier Motion Processing in the Optic Tectum and Pretectum of the Zebrafish Larva.},
 type = {article},
 year = {2021},
 keywords = {Fourier motion,neuronal circuit dynamics,two-photon calcium imaging,visual system,zebrafish},
 pages = {814128},
 volume = {15},
 websites = {https://www.frontiersin.org/articles/10.3389/fncir.2021.814128/full},
 month = {1},
 day = {7},
 id = {490021be-4c8c-3245-9ead-819d965833eb},
 created = {2022-01-07T15:25:53.253Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2022-04-22T22:23:00.380Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Duchemin2022},
 private_publication = {false},
 abstract = {In the presence of moving visual stimuli, the majority of animals follow the Fourier motion energy (luminance), independently of other stimulus features (edges, contrast, etc.). While the behavioral response to Fourier motion has been studied in the past, how Fourier motion is represented and processed by sensory brain areas remains elusive. Here, we investigated how visual moving stimuli with or without the first Fourier component (square-wave signal or missing fundamental signal) are represented in the main visual regions of the zebrafish brain. First, we monitored the larva's optokinetic response (OKR) induced by square-wave and missing fundamental signals. Then, we used two-photon microscopy and GCaMP6f zebrafish larvae to monitor neuronal circuit dynamics in the optic tectum and the pretectum. We observed that both the optic tectum and the pretectum circuits responded to the square-wave gratings. However, only the pretectum responded specifically to the direction of the missing-fundamental signal. In addition, a group of neurons in the pretectum responded to the direction of the behavioral output (OKR), independently of the type of stimulus presented. Our results suggest that the optic tectum responds to the different features of the stimulus (e.g., contrast, spatial frequency, direction, etc.), but does not respond to the direction of motion if the motion information is not coherent (e.g., the luminance and the edges and contrast in the missing-fundamental signal). On the other hand, the pretectum mainly responds to the motion of the stimulus based on the Fourier energy.},
 bibtype = {article},
 author = {Duchemin, Auriane and Privat, Martin and Sumbre, Germán},
 doi = {10.3389/fncir.2021.814128},
 journal = {Frontiers in neural circuits},
 number = {January}
}

In the presence of moving visual stimuli, the majority of animals follow the Fourier motion energy (luminance), independently of other stimulus features (edges, contrast, etc.). While the behavioral response to Fourier motion has been studied in the past, how Fourier motion is represented and processed by sensory brain areas remains elusive. Here, we investigated how visual moving stimuli with or without the first Fourier component (square-wave signal or missing fundamental signal) are represented in the main visual regions of the zebrafish brain. First, we monitored the larva's optokinetic response (OKR) induced by square-wave and missing fundamental signals. Then, we used two-photon microscopy and GCaMP6f zebrafish larvae to monitor neuronal circuit dynamics in the optic tectum and the pretectum. We observed that both the optic tectum and the pretectum circuits responded to the square-wave gratings. However, only the pretectum responded specifically to the direction of the missing-fundamental signal. In addition, a group of neurons in the pretectum responded to the direction of the behavioral output (OKR), independently of the type of stimulus presented. Our results suggest that the optic tectum responds to the different features of the stimulus (e.g., contrast, spatial frequency, direction, etc.), but does not respond to the direction of motion if the motion information is not coherent (e.g., the luminance and the edges and contrast in the missing-fundamental signal). On the other hand, the pretectum mainly responds to the motion of the stimulus based on the Fourier energy.

@article{
 title = {Naturalistic Behavior: The Zebrafish Larva Strikes Back},
 type = {article},
 year = {2020},
 pages = {R27-R29},
 volume = {30},
 websites = {https://www-cell-com.insb.bib.cnrs.fr/current-biology/fulltext/S0960-9822(19)31453-8},
 month = {1},
 publisher = {Elsevier},
 day = {6},
 id = {cb8d2fae-5187-339d-8f5e-c3c9accd1fa0},
 created = {2020-01-06T15:58:02.374Z},
 accessed = {2020-01-06},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2021-08-30T07:50:52.199Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Two recent studies show that zebrafish larvae alternate between two behavioral modes: exploration and hunting. Both behaviors are structured on multiple time scales, and require the integration of internal and external cues to generate sequences of stereotyped swimming movements.},
 bibtype = {article},
 author = {Privat, Martin and Sumbre, Germán},
 doi = {10.1016/j.cub.2019.11.014},
 journal = {Current Biology},
 number = {1}
}

Two recent studies show that zebrafish larvae alternate between two behavioral modes: exploration and hunting. Both behaviors are structured on multiple time scales, and require the integration of internal and external cues to generate sequences of stereotyped swimming movements.

@article{
 title = {An open-source and low-cost feeding system for zebrafish facilities},
 type = {article},
 year = {2019},
 pages = {1-15},
 websites = {https://www.biorxiv.org/content/10.1101/558205v1},
 month = {2},
 id = {5f1c1535-b0cc-3cc9-a8b5-a172c31d5195},
 created = {2019-03-14T08:44:11.419Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2019-11-07T22:37:58.652Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Zebrafish is an established animal model used in the fields of developmental biology and genetics for more than 60 years, and among the first models to become genetically tractable. More recently, zebrafish has also become a model of reference for human diseases and systems neuroscience. The current extensive use of zebrafish in research and pharmaceutical companies promoted the development of several commercial husbandry systems specially designed for zebrafish. However, feeding is still a challenging and arduous task that can result in occupational disorders of the personnel working at the zebrafish facilities (e.g. tendinitis, back pain, etc.). To palliate these risks, a commercial robotic approach has been developed, yet its expensive cost makes this solution accessible only to very large fish facilities. Most mid-size and small facilities with limited resources still use manual feeding methods. Here, we propose two custom-made open-source semi-automatic feeding systems for dry and live food, capable of preventing and/or alleviating occupational disorders, improve feeding accuracy and decrease feeding time. Both systems are designed for mid-size or small fish facilities. They are cheap and can be easily and rapidly built using 3D printing and standard electronic and lab components.},
 bibtype = {article},
 author = {Tangara, Astou and Paresys, Gerard and Bouallague, Firas and Cabirou, Yvon and Fodor, Jozsua and Llobet, Victor and Sumbre, German},
 doi = {https://doi.org/10.1101/558205v1},
 journal = {bioRxiv}
}

Zebrafish is an established animal model used in the fields of developmental biology and genetics for more than 60 years, and among the first models to become genetically tractable. More recently, zebrafish has also become a model of reference for human diseases and systems neuroscience. The current extensive use of zebrafish in research and pharmaceutical companies promoted the development of several commercial husbandry systems specially designed for zebrafish. However, feeding is still a challenging and arduous task that can result in occupational disorders of the personnel working at the zebrafish facilities (e.g. tendinitis, back pain, etc.). To palliate these risks, a commercial robotic approach has been developed, yet its expensive cost makes this solution accessible only to very large fish facilities. Most mid-size and small facilities with limited resources still use manual feeding methods. Here, we propose two custom-made open-source semi-automatic feeding systems for dry and live food, capable of preventing and/or alleviating occupational disorders, improve feeding accuracy and decrease feeding time. Both systems are designed for mid-size or small fish facilities. They are cheap and can be easily and rapidly built using 3D printing and standard electronic and lab components.

@article{
 title = {Functional Integration of Newborn Neurons in the Zebrafish Optic Tectum},
 type = {article},
 year = {2019},
 keywords = {activity-dependent development,neurogenesis,newborn neurons,optic tectum,visual system,zebrafish},
 pages = {57},
 volume = {7},
 websites = {https://www.frontiersin.org/article/10.3389/fcell.2019.00057/full},
 month = {4},
 publisher = {Frontiers},
 day = {16},
 id = {f4b8c3b5-58ad-3d36-9c79-89f516a6a8c1},
 created = {2019-04-16T21:59:07.903Z},
 accessed = {2019-04-04},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2020-01-08T13:02:45.211Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Neurogenesis persists during adulthood in restricted parts of the vertebrate brain. In the optic tectum (OT) of the zebrafish larva, newborn neurons are continuously added and contribute to visual information processing. Recent studies have started to describe the functional development and fate of newborn neurons in the OT. Like the mammalian brain, newborn neurons in the OT require sensory inputs for their integration into local networks and survival. Recent findings suggest that the functional development of newborn neurons requires both activity-dependent and hard-wired mechanisms for proper circuit integration. Here, we review these findings and argue that the study of neurogenesis in non-mammalian species will help elucidate the general mechanisms of circuit assembly following neurogenesis.},
 bibtype = {article},
 author = {Boulanger-Weill, Jonathan and Sumbre, Germán},
 doi = {10.3389/fcell.2019.00057},
 journal = {Frontiers in Cell and Developmental Biology}
}

Neurogenesis persists during adulthood in restricted parts of the vertebrate brain. In the optic tectum (OT) of the zebrafish larva, newborn neurons are continuously added and contribute to visual information processing. Recent studies have started to describe the functional development and fate of newborn neurons in the OT. Like the mammalian brain, newborn neurons in the OT require sensory inputs for their integration into local networks and survival. Recent findings suggest that the functional development of newborn neurons requires both activity-dependent and hard-wired mechanisms for proper circuit integration. Here, we review these findings and argue that the study of neurogenesis in non-mammalian species will help elucidate the general mechanisms of circuit assembly following neurogenesis.

@article{
 title = {Sensorimotor Transformations in the Zebrafish Auditory System.},
 type = {article},
 year = {2019},
 keywords = {audition,behavior,neuronal circuit dynamics,sensorimotor transformations,two-photon calcium imaging,zebrafish larva},
 pages = {4010-4023.e4},
 volume = {29},
 websites = {https://linkinghub.elsevier.com/retrieve/pii/S0960982219313600},
 month = {12},
 day = {2},
 id = {3306c232-c7a3-3516-96bb-b0f36ab3099e},
 created = {2019-11-07T21:12:54.389Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2019-12-24T23:36:37.407Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Privat2019},
 private_publication = {false},
 abstract = {Organisms use their sensory systems to acquire information from their environment and integrate this information to produce relevant behaviors. Nevertheless, how sensory information is converted into adequate motor patterns in the brain remains an open question. Here, we addressed this question using two-photon and light-sheet calcium imaging in intact, behaving zebrafish larvae. We monitored neural activity elicited by auditory stimuli while simultaneously recording tail movements. We observed a spatial organization of neural activity according to four different response profiles (frequency tuning curves), suggesting a low-dimensional representation of frequency information, maintained throughout the development of the larvae. Low frequencies (150-450 Hz) were locally processed in the hindbrain and elicited motor behaviors. In contrast, higher frequencies (900-1,000 Hz) rarely induced motor behaviors and were also represented in the midbrain. Finally, we found that the sensorimotor transformations in the zebrafish auditory system are a continuous and gradual process that involves the temporal integration of the sensory response in order to generate a motor behavior.},
 bibtype = {article},
 author = {Privat, Martin and Romano, Sebastián A. and Pietri, Thomas and Jouary, Adrien and Boulanger-Weill, Jonathan and Elbaz, Nicolas and Duchemin, Auriane and Soares, Daphne and Sumbre, Germán},
 doi = {10.1016/j.cub.2019.10.020},
 journal = {Current Biology},
 number = {23}
}

Organisms use their sensory systems to acquire information from their environment and integrate this information to produce relevant behaviors. Nevertheless, how sensory information is converted into adequate motor patterns in the brain remains an open question. Here, we addressed this question using two-photon and light-sheet calcium imaging in intact, behaving zebrafish larvae. We monitored neural activity elicited by auditory stimuli while simultaneously recording tail movements. We observed a spatial organization of neural activity according to four different response profiles (frequency tuning curves), suggesting a low-dimensional representation of frequency information, maintained throughout the development of the larvae. Low frequencies (150-450 Hz) were locally processed in the hindbrain and elicited motor behaviors. In contrast, higher frequencies (900-1,000 Hz) rarely induced motor behaviors and were also represented in the midbrain. Finally, we found that the sensorimotor transformations in the zebrafish auditory system are a continuous and gradual process that involves the temporal integration of the sensory response in order to generate a motor behavior.

@article{
 title = {Principles of Functional Circuit Connectivity: Insights From Spontaneous Activity in the Zebrafish Optic Tectum},
 type = {article},
 year = {2018},
 keywords = {Zebrafish,functional connectivity,optic tectum,sensory experience,spontaneous activity,two-photon calcium imaging},
 pages = {1-8},
 volume = {12},
 websites = {https://www.frontiersin.org/article/10.3389/fncir.2018.00046/full},
 month = {6},
 publisher = {Frontiers},
 day = {21},
 id = {cb410613-5043-3c11-9e95-336c8b1733c0},
 created = {2018-06-21T10:38:27.692Z},
 accessed = {2018-06-21},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2018-11-21T14:36:49.060Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Marachlian2018},
 private_publication = {false},
 abstract = {The brain is continuously active, even in the absence of external stimulation. In the optic tectum of the zebrafish larva, this spontaneous activity is spatially organized and reflects the circuit’s functional connectivity. The structure of the spontaneous activity displayed patterns associated with aspects of the larva’s preferences when engaging in complex visuo-motor behaviors, suggesting that the tectal circuit is adapted for the circuit’s functional role in detecting visual cues and generating adequate motor behaviors. Further studies in sensory deprived larvae suggest that the basic structure of the functional connectivity patterns emerges even in the absence of retinal inputs, but that its fine structure is affected by visual experience.},
 bibtype = {article},
 author = {Marachlian, Emiliano and Avitan, Lilach and Goodhill, Geoffrey J. and Sumbre, Germán},
 doi = {10.3389/fncir.2018.00046},
 journal = {Frontiers in Neural Circuits},
 number = {June}
}

The brain is continuously active, even in the absence of external stimulation. In the optic tectum of the zebrafish larva, this spontaneous activity is spatially organized and reflects the circuit’s functional connectivity. The structure of the spontaneous activity displayed patterns associated with aspects of the larva’s preferences when engaging in complex visuo-motor behaviors, suggesting that the tectal circuit is adapted for the circuit’s functional role in detecting visual cues and generating adequate motor behaviors. Further studies in sensory deprived larvae suggest that the basic structure of the functional connectivity patterns emerges even in the absence of retinal inputs, but that its fine structure is affected by visual experience.

@article{
 title = {Whole-Brain Neuronal Activity Displays Crackling Noise Dynamics},
 type = {article},
 year = {2018},
 keywords = {GcaMP,calcium imaging,gap junctions,light-sheet microscopy,motor behavior,phase transitions,scale invariance,sensory modulation,whole-brain dynamics,zebrafish},
 pages = {1446-1459.e6},
 volume = {100},
 websites = {https://linkinghub.elsevier.com/retrieve/pii/S089662731830953X},
 month = {12},
 publisher = {Elsevier},
 day = {15},
 id = {b1c4c94e-6063-39ec-92f1-de59a0767c51},
 created = {2018-11-15T21:27:17.817Z},
 accessed = {2018-11-15},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2018-12-19T21:12:21.023Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Ponce-Alvarez2018},
 private_publication = {false},
 abstract = {Previous studies suggest that the brain operates at a critical point in which phases of order and disorder coexist, producing emergent patterned dynamics at all scales and optimizing several brain functions. Here, we combined light-sheet microscopy with GCaMP zebrafish larvae to study whole-brain dynamics in vivo at near single-cell resolution. We show that spontaneous activity propagates in the brain's three-dimensional space, generating scale-invariant neuronal avalanches with time courses and recurrence times that exhibit statistical self-similarity at different magnitude, temporal, and frequency scales. This suggests that the nervous system operates close to a non-equilibrium phase transition, where a large repertoire of spatial, temporal, and interactive modes can be supported. Finally, we show that gap junctions contribute to the maintenance of criticality and that, during interactions with the environment (sensory inputs and self-generated behaviors), the system is transiently displaced to a more ordered regime, conceivably to limit the potential sensory representations and motor outcomes.},
 bibtype = {article},
 author = {Ponce-Alvarez, Adrián and Jouary, Adrien and Privat, Martin and Deco, Gustavo and Sumbre, Germán},
 doi = {10.1016/j.neuron.2018.10.045},
 journal = {Neuron},
 number = {6}
}

Previous studies suggest that the brain operates at a critical point in which phases of order and disorder coexist, producing emergent patterned dynamics at all scales and optimizing several brain functions. Here, we combined light-sheet microscopy with GCaMP zebrafish larvae to study whole-brain dynamics in vivo at near single-cell resolution. We show that spontaneous activity propagates in the brain's three-dimensional space, generating scale-invariant neuronal avalanches with time courses and recurrence times that exhibit statistical self-similarity at different magnitude, temporal, and frequency scales. This suggests that the nervous system operates close to a non-equilibrium phase transition, where a large repertoire of spatial, temporal, and interactive modes can be supported. Finally, we show that gap junctions contribute to the maintenance of criticality and that, during interactions with the environment (sensory inputs and self-generated behaviors), the system is transiently displaced to a more ordered regime, conceivably to limit the potential sensory representations and motor outcomes.

@article{
 title = {A computational toolbox and step-by-step tutorial for the analysis of neuronal population dynamics in calcium imaging data},
 type = {article},
 year = {2017},
 pages = {1-36},
 websites = {http://biorxiv.org/content/early/2017/04/02/103879},
 month = {4},
 id = {309aae0b-3053-3cd3-ba62-16ba0a82a183},
 created = {2017-01-30T08:33:22.000Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2020-01-23T10:24:17.094Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Romano2017},
 private_publication = {false},
 abstract = {The development of new imaging and optogenetics techniques to study the dynamics of large neuronal circuits is generating datasets of unprecedented volume and complexity, demanding the development of appropriate analysis tools. We present a tutorial for the use of a comprehensive computational toolbox for the analysis of neuronal population activity imaging. It consists of tools for image pre-processing and segmentation, estimation of significant single-neuron single-trial signals, mapping event-related neuronal responses, detection of activity-correlated neuronal clusters, exploration of population dynamics, and analysis of clusters' features against surrogate control datasets. They are integrated in a modular and versatile processing pipeline, adaptable to different needs. The clustering module is capable of detecting flexible, dynamically activated neuronal assemblies, consistent with the distributed population coding of the brain. We demonstrate the suitability of the toolbox for a variety of calcium imaging datasets, and provide a case study to explain its implementation.},
 bibtype = {article},
 author = {Romano, Sebastián A and Pérez-schuster, Verónica and Jouary, Adrien and Candeo, Alessia and Boulanger-Weill, Jonathan and Sumbre, Germán},
 doi = {https://doi.org/10.1101/103879},
 journal = {bioRxiv}
}

The development of new imaging and optogenetics techniques to study the dynamics of large neuronal circuits is generating datasets of unprecedented volume and complexity, demanding the development of appropriate analysis tools. We present a tutorial for the use of a comprehensive computational toolbox for the analysis of neuronal population activity imaging. It consists of tools for image pre-processing and segmentation, estimation of significant single-neuron single-trial signals, mapping event-related neuronal responses, detection of activity-correlated neuronal clusters, exploration of population dynamics, and analysis of clusters' features against surrogate control datasets. They are integrated in a modular and versatile processing pipeline, adaptable to different needs. The clustering module is capable of detecting flexible, dynamically activated neuronal assemblies, consistent with the distributed population coding of the brain. We demonstrate the suitability of the toolbox for a variety of calcium imaging datasets, and provide a case study to explain its implementation.

@article{
 title = {Functional Interactions between Newborn and Mature Neurons Leading to Integration into Established Neuronal Circuits.},
 type = {article},
 year = {2017},
 keywords = {neurogenesis,newborn neurons,optic tectum,optogenetics,two-photon calcium imaging,visual system,zebrafish},
 pages = {1707-1720.e5},
 volume = {27},
 websites = {http://linkinghub.elsevier.com/retrieve/pii/S0960982217305651,http://www.ncbi.nlm.nih.gov/pubmed/28578928,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5483231},
 month = {6},
 day = {19},
 id = {ee5d4e60-6937-338b-ada4-6d2be37fa13c},
 created = {2017-06-19T18:23:49.193Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2021-05-31T18:57:14.380Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Boulanger-Weill2017a},
 private_publication = {false},
 abstract = {From development up to adulthood, the vertebrate brain is continuously supplied with newborn neurons that integrate into established mature circuits. However, how this process is coordinated during development remains unclear. Using two-photon imaging, GCaMP5 transgenic zebrafish larvae, and sparse electroporation in the larva's optic tectum, we monitored spontaneous and induced activity of large neuronal populations containing newborn and functionally mature neurons. We observed that the maturation of newborn neurons is a 4-day process. Initially, newborn neurons showed undeveloped dendritic arbors, no neurotransmitter identity, and were unresponsive to visual stimulation, although they displayed spontaneous calcium transients. Later on, newborn-labeled neurons began to respond to visual stimuli but in a very variable manner. At the end of the maturation period, newborn-labeled neurons exhibited visual tuning curves (spatial receptive fields and direction selectivity) and spontaneous correlated activity with neighboring functionally mature neurons. At this developmental stage, newborn-labeled neurons presented complex dendritic arbors and neurotransmitter identity (excitatory or inhibitory). Removal of retinal inputs significantly perturbed the integration of newborn neurons into the functionally mature tectal network. Our results provide a comprehensive description of the maturation of newborn neurons during development and shed light on potential mechanisms underlying their integration into a functionally mature neuronal circuit.},
 bibtype = {article},
 author = {Boulanger-Weill, Jonathan and Candat, Virginie and Jouary, Adrien and Romano, Sebastián A. and Pérez-Schuster, Verónica and Sumbre, Germán},
 doi = {10.1016/j.cub.2017.05.029},
 journal = {Current Biology},
 number = {12}
}

From development up to adulthood, the vertebrate brain is continuously supplied with newborn neurons that integrate into established mature circuits. However, how this process is coordinated during development remains unclear. Using two-photon imaging, GCaMP5 transgenic zebrafish larvae, and sparse electroporation in the larva's optic tectum, we monitored spontaneous and induced activity of large neuronal populations containing newborn and functionally mature neurons. We observed that the maturation of newborn neurons is a 4-day process. Initially, newborn neurons showed undeveloped dendritic arbors, no neurotransmitter identity, and were unresponsive to visual stimulation, although they displayed spontaneous calcium transients. Later on, newborn-labeled neurons began to respond to visual stimuli but in a very variable manner. At the end of the maturation period, newborn-labeled neurons exhibited visual tuning curves (spatial receptive fields and direction selectivity) and spontaneous correlated activity with neighboring functionally mature neurons. At this developmental stage, newborn-labeled neurons presented complex dendritic arbors and neurotransmitter identity (excitatory or inhibitory). Removal of retinal inputs significantly perturbed the integration of newborn neurons into the functionally mature tectal network. Our results provide a comprehensive description of the maturation of newborn neurons during development and shed light on potential mechanisms underlying their integration into a functionally mature neuronal circuit.

@article{
 title = {An integrated calcium imaging processing toolbox for the analysis of neuronal population dynamics},
 type = {article},
 year = {2017},
 pages = {e1005526},
 volume = {13},
 websites = {http://dx.plos.org/10.1371/journal.pcbi.1005526,https://dx.plos.org/10.1371/journal.pcbi.1005526},
 month = {6},
 day = {7},
 id = {cdccce61-8418-3e70-999c-22b3a4b8cb9a},
 created = {2018-05-30T14:04:03.430Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2020-01-08T13:02:45.152Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Romano2017c},
 private_publication = {false},
 abstract = {The development of new imaging and optogenetics techniques to study the dynamics of large neuronal circuits is generating datasets of unprecedented volume and complexity, demanding the development of appropriate analysis tools. We present a comprehensive computational workflow for the analysis of neuronal population calcium dynamics. The toolbox includes newly developed algorithms and interactive tools for image pre-processing and segmentation, estimation of significant single-neuron single-trial signals, mapping event-related neuronal responses, detection of activity-correlated neuronal clusters, exploration of population dynamics, and analysis of clusters' features against surrogate control datasets. The modules are integrated in a modular and versatile processing pipeline, adaptable to different needs. The clustering module is capable of detecting flexible, dynamically activated neuronal assemblies, consistent with the distributed population coding of the brain. We demonstrate the suitability of the toolbox for a variety of calcium imaging datasets. The toolbox open-source code, a step-by-step tutorial and a case study dataset are available at https://github.com/zebrain-lab/Toolbox-Romano-et-al.},
 bibtype = {article},
 author = {Romano, Sebastián A. and Pérez-Schuster, Verónica and Jouary, Adrien and Boulanger-Weill, Jonathan and Candeo, Alessia and Pietri, Thomas and Sumbre, Germán},
 editor = {Graham, Lyle J.},
 doi = {10.1371/journal.pcbi.1005526},
 journal = {PLOS Computational Biology},
 number = {6}
}

The development of new imaging and optogenetics techniques to study the dynamics of large neuronal circuits is generating datasets of unprecedented volume and complexity, demanding the development of appropriate analysis tools. We present a comprehensive computational workflow for the analysis of neuronal population calcium dynamics. The toolbox includes newly developed algorithms and interactive tools for image pre-processing and segmentation, estimation of significant single-neuron single-trial signals, mapping event-related neuronal responses, detection of activity-correlated neuronal clusters, exploration of population dynamics, and analysis of clusters' features against surrogate control datasets. The modules are integrated in a modular and versatile processing pipeline, adaptable to different needs. The clustering module is capable of detecting flexible, dynamically activated neuronal assemblies, consistent with the distributed population coding of the brain. We demonstrate the suitability of the toolbox for a variety of calcium imaging datasets. The toolbox open-source code, a step-by-step tutorial and a case study dataset are available at https://github.com/zebrain-lab/Toolbox-Romano-et-al.

@article{
 title = {The Emergence of the Spatial Structure of Tectal Spontaneous Activity Is Independent of Visual Inputs},
 type = {article},
 year = {2017},
 keywords = {behavior,development of spontaneous activity,neuronal circuit dynamics,optic tectum,retinal input,visual system,zebrafish},
 pages = {939-948},
 volume = {19},
 websites = {http://linkinghub.elsevier.com/retrieve/pii/S2211124717304904},
 month = {5},
 day = {2},
 id = {bb155f21-9711-3730-8cd5-fbd6310de8ed},
 created = {2018-06-12T13:03:11.492Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2020-01-13T12:20:13.609Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Pietri2017},
 private_publication = {false},
 abstract = {The brain is spontaneously active, even in the absence of sensory stimulation. The functionally mature zebrafish optic tectum shows spontaneous activity patterns reflecting a functional connectivity adapted for the circuit's functional role and predictive of behavior. However, neither the emergence of these patterns during development nor the role of retinal inputs in their maturation has been characterized. Using two-photon calcium imaging, we analyzed spontaneous activity in intact and enucleated zebrafish larvae throughout tectum development. At the onset of retinotectal connections, intact larvae showed major changes in the spatiotemporal structure of spontaneous activity. Although the absence of retinal inputs had a significant impact on the development of the temporal structure, the tectum was still capable of developing a spatial structure associated with the circuit's functional roles and predictive of behavior. We conclude that neither visual experience nor intrinsic retinal activity is essential for the emergence of a spatially structured functional circuit.},
 bibtype = {article},
 author = {Pietri, Thomas and Romano, Sebastián A. and Pérez-Schuster, Verónica and Boulanger-Weill, Jonathan and Candat, Virginie and Sumbre, Germán},
 doi = {10.1016/j.celrep.2017.04.015},
 journal = {Cell Reports},
 number = {5}
}

The brain is spontaneously active, even in the absence of sensory stimulation. The functionally mature zebrafish optic tectum shows spontaneous activity patterns reflecting a functional connectivity adapted for the circuit's functional role and predictive of behavior. However, neither the emergence of these patterns during development nor the role of retinal inputs in their maturation has been characterized. Using two-photon calcium imaging, we analyzed spontaneous activity in intact and enucleated zebrafish larvae throughout tectum development. At the onset of retinotectal connections, intact larvae showed major changes in the spatiotemporal structure of spontaneous activity. Although the absence of retinal inputs had a significant impact on the development of the temporal structure, the tectum was still capable of developing a spatial structure associated with the circuit's functional roles and predictive of behavior. We conclude that neither visual experience nor intrinsic retinal activity is essential for the emergence of a spatially structured functional circuit.

@article{
 title = {Automatic classification of behavior in zebrafish larva},
 type = {article},
 year = {2016},
 pages = {1-14},
 websites = {http://biorxiv.org/content/early/2016/05/10/052324},
 month = {5},
 id = {4427a90b-6883-3395-a816-f90305a2660e},
 created = {2017-01-30T08:33:22.000Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2019-09-26T14:44:45.738Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Jouary2016},
 private_publication = {false},
 abstract = {Zebrafish larvae navigate the environment by discrete episode of propulsion called bouts. We introduce a novel method for automatically classifying zebrafish tail movements. We used a supervised soft-clustering algorithm to categorize tail bouts into 5 categories of movements: Scoot, Asymmetrical Scoot, Routine Turn, C Bend and Burst. Tail bouts were correctly classified with 82% chance while errors in the classification occurred mostly between similar categories. Although previous studies have performed categorization of behavior in free-swimming conditions, our method does not rely on the analysis of the trajectories and can be applied in both head-fixed and free-swimming conditions.},
 bibtype = {article},
 author = {Jouary, Adrien and Sumbre, German},
 doi = {10.1101/052324},
 journal = {bioRxiv}
}

Zebrafish larvae navigate the environment by discrete episode of propulsion called bouts. We introduce a novel method for automatically classifying zebrafish tail movements. We used a supervised soft-clustering algorithm to categorize tail bouts into 5 categories of movements: Scoot, Asymmetrical Scoot, Routine Turn, C Bend and Burst. Tail bouts were correctly classified with 82% chance while errors in the classification occurred mostly between similar categories. Although previous studies have performed categorization of behavior in free-swimming conditions, our method does not rely on the analysis of the trajectories and can be applied in both head-fixed and free-swimming conditions.

@article{
 title = {A 2D virtual reality system for visual goal-driven navigation in zebrafish larvae},
 type = {article},
 year = {2016},
 pages = {34015},
 volume = {6},
 websites = {http://www.nature.com/articles/srep34015},
 month = {9},
 publisher = {Nature Publishing Group},
 day = {23},
 id = {9c2d8cef-99d2-3090-a37d-72f83fe152b8},
 created = {2018-06-12T14:21:54.329Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2020-01-08T13:16:04.431Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Sumbre2016},
 private_publication = {false},
 abstract = {Animals continuously rely on sensory feedback to adjust motor commands. In order to study the role of visual feedback in goal-driven navigation, we developed a 2D visual virtual reality system for zebrafish larvae. The visual feedback can be set to be similar to what the animal experiences in natural conditions. Alternatively, modification of the visual feedback can be used to study how the brain adapts to perturbations. For this purpose, we first generated a library of free-swimming behaviors from which we learned the relationship between the trajectory of the larva and the shape of its tail. Then, we used this technique to infer the intended displacements of head-fixed larvae, and updated the visual environment accordingly. Under these conditions, larvae were capable of aligning and swimming in the direction of a whole-field moving stimulus and produced the fine changes in orientation and position required to capture virtual prey. We demonstrate the sensitivity of larvae to visual feedback by updating the visual world in real-time or only at the end of the discrete swimming episodes. This visual feedback perturbation caused impaired performance of prey-capture behavior, suggesting that larvae rely on continuous visual feedback during swimming.},
 bibtype = {article},
 author = {Jouary, Adrien and Haudrechy, Mathieu and Candelier, Raphaël and Sumbre, German},
 doi = {10.1038/srep34015},
 journal = {Scientific Reports},
 number = {1}
}

Animals continuously rely on sensory feedback to adjust motor commands. In order to study the role of visual feedback in goal-driven navigation, we developed a 2D visual virtual reality system for zebrafish larvae. The visual feedback can be set to be similar to what the animal experiences in natural conditions. Alternatively, modification of the visual feedback can be used to study how the brain adapts to perturbations. For this purpose, we first generated a library of free-swimming behaviors from which we learned the relationship between the trajectory of the larva and the shape of its tail. Then, we used this technique to infer the intended displacements of head-fixed larvae, and updated the visual environment accordingly. Under these conditions, larvae were capable of aligning and swimming in the direction of a whole-field moving stimulus and produced the fine changes in orientation and position required to capture virtual prey. We demonstrate the sensitivity of larvae to visual feedback by updating the visual world in real-time or only at the end of the discrete swimming episodes. This visual feedback perturbation caused impaired performance of prey-capture behavior, suggesting that larvae rely on continuous visual feedback during swimming.

@article{
 title = {Sustained Rhythmic Brain Activity Underlies Visual Motion Perception in Zebrafish},
 type = {article},
 year = {2016},
 keywords = {GCaMP,eye movements,mathematical modeling,motion aftereffect,neuronal circuit dynamics,optogenetics,two-photon calcium imaging,visual illusions,visual motion perception,zebrafish},
 pages = {1098-1112},
 volume = {17},
 websites = {http://linkinghub.elsevier.com/retrieve/pii/S2211124716313213},
 month = {10},
 publisher = {Cell Press},
 day = {18},
 id = {9fc8b6b4-13cc-3e40-a6ff-73909a2a44a7},
 created = {2018-12-27T19:21:24.922Z},
 accessed = {2018-11-23},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2020-01-08T12:58:46.088Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Perez-Schuster2016},
 source_type = {article},
 private_publication = {false},
 abstract = {Following moving visual stimuli (conditioning stimuli, CS), many organisms perceive, in the absence of physical stimuli, illusory motion in the opposite direction. This phenomenon is known as the motion aftereffect (MAE). Here, we use MAE as a tool to study the neuronal basis of visual motion perception in zebrafish larvae. Using zebrafish eye movements as an indicator of visual motion perception, we find that larvae perceive MAE. Blocking eye movements using optogenetics during CS presentation did not affect MAE, but tectal ablation significantly weakened it. Using two-photon calcium imaging of behaving GCaMP3 larvae, we find post-stimulation sustained rhythmic activity among direction-selective tectal neurons associated with the perception of MAE. In addition, tectal neurons tuned to the CS direction habituated, but neurons in the retina did not. Finally, a model based on competition between direction-selective neurons reproduced MAE, suggesting a neuronal circuit capable of generating perception of visual motion.},
 bibtype = {article},
 author = {Pérez-Schuster, Verónica and Kulkarni, Anirudh and Nouvian, Morgane and Romano, Sebastián A. and Lygdas, Konstantinos and Jouary, Adrien and Dipoppa, Mario and Pietri, Thomas and Haudrechy, Mathieu and Candat, Virginie and Boulanger-Weill, Jonathan and Hakim, Vincent and Sumbre, Germán},
 doi = {10.1016/j.celrep.2016.09.065},
 journal = {Cell Reports},
 number = {4}
}

Following moving visual stimuli (conditioning stimuli, CS), many organisms perceive, in the absence of physical stimuli, illusory motion in the opposite direction. This phenomenon is known as the motion aftereffect (MAE). Here, we use MAE as a tool to study the neuronal basis of visual motion perception in zebrafish larvae. Using zebrafish eye movements as an indicator of visual motion perception, we find that larvae perceive MAE. Blocking eye movements using optogenetics during CS presentation did not affect MAE, but tectal ablation significantly weakened it. Using two-photon calcium imaging of behaving GCaMP3 larvae, we find post-stimulation sustained rhythmic activity among direction-selective tectal neurons associated with the perception of MAE. In addition, tectal neurons tuned to the CS direction habituated, but neurons in the retina did not. Finally, a model based on competition between direction-selective neurons reproduced MAE, suggesting a neuronal circuit capable of generating perception of visual motion.

@article{
 title = {A microfluidic device to study neuronal and motor responses to acute chemical stimuli in zebrafish},
 type = {article},
 year = {2015},
 pages = {12196},
 volume = {5},
 websites = {http://www.nature.com/articles/srep12196},
 month = {12},
 publisher = {Nature Publishing Group},
 day = {21},
 id = {731aef52-346e-3c3d-a0f0-c100c763c549},
 created = {2018-05-30T14:04:03.477Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2020-01-08T13:02:45.260Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Candelier2015a},
 private_publication = {false},
 abstract = {Zebrafish larva is a unique model for whole-brain functional imaging and to study sensory-motor integration in the vertebrate brain. To take full advantage of this system, one needs to design sensory environments that can mimic the complex spatiotemporal stimulus patterns experienced by the animal in natural conditions. We report on a novel open-ended microfluidic device that delivers pulses of chemical stimuli to agarose-restrained larvae with near-millisecond switching rate and unprecedented spatial and concentration accuracy and reproducibility. In combination with two-photon calcium imaging and recordings of tail movements, we found that stimuli of opposite hedonic values induced different circuit activity patterns. Moreover, by precisely controlling the duration of the stimulus (50-500 ms), we found that the probability of generating a gustatory-induced behavior is encoded by the number of neurons activated. This device may open new ways to dissect the neural-circuit principles underlying chemosensory perception.},
 bibtype = {article},
 author = {Candelier, Raphaël and Sriti Murmu, Meena and Alejo Romano, Sebastián and Jouary, Adrien and Debrégeas, Georges and Sumbre, Germán},
 doi = {10.1038/srep12196},
 journal = {Scientific Reports},
 number = {1}
}

Zebrafish larva is a unique model for whole-brain functional imaging and to study sensory-motor integration in the vertebrate brain. To take full advantage of this system, one needs to design sensory environments that can mimic the complex spatiotemporal stimulus patterns experienced by the animal in natural conditions. We report on a novel open-ended microfluidic device that delivers pulses of chemical stimuli to agarose-restrained larvae with near-millisecond switching rate and unprecedented spatial and concentration accuracy and reproducibility. In combination with two-photon calcium imaging and recordings of tail movements, we found that stimuli of opposite hedonic values induced different circuit activity patterns. Moreover, by precisely controlling the duration of the stimulus (50-500 ms), we found that the probability of generating a gustatory-induced behavior is encoded by the number of neurons activated. This device may open new ways to dissect the neural-circuit principles underlying chemosensory perception.

@article{
 title = {Spontaneous neuronal network dynamics reveal circuit's functional adaptations for behavior.},
 type = {article},
 year = {2015},
 pages = {1070-85},
 volume = {85},
 websites = {http://linkinghub.elsevier.com/retrieve/pii/S0896627315000537},
 month = {3},
 day = {4},
 id = {0c6ab53e-6e25-339d-ac1f-04470c4debaf},
 created = {2018-06-12T14:21:54.311Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2019-09-20T10:02:07.237Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Romano2015c},
 private_publication = {false},
 abstract = {Spontaneous neuronal activity is spatiotemporally structured, influencing brain computations. Nevertheless, the neuronal interactions underlying these spontaneous activity patterns, and their biological relevance, remain elusive. Here, we addressed these questions using two-photon calcium imaging of intact zebrafish larvae to monitor the neuron-to-neuron spontaneous activity fine structure in the tectum, a region involved in visual spatial detection. Spontaneous activity was organized in topographically compact assemblies, grouping functionally similar neurons rather than merely neighboring ones, reflecting the tectal retinotopic map despite being independent of retinal drive. Assemblies represent all-or-none-like sub-networks shaped by competitive dynamics, mechanisms advantageous for visual detection in noisy natural environments. Notably, assemblies were tuned to the same angular sizes and spatial positions as prey-detection performance in behavioral assays, and their spontaneous activation predicted directional tail movements. Therefore, structured spontaneous activity represents "preferred" network states, tuned to behaviorally relevant features, emerging from the circuit's intrinsic non-linear dynamics, adapted for its functional role.},
 bibtype = {article},
 author = {Romano, Sebastián A. and Pietri, Thomas and Pérez-Schuster, Verónica and Jouary, Adrien and Haudrechy, Mathieu and Sumbre, Germán},
 doi = {10.1016/j.neuron.2015.01.027},
 journal = {Neuron},
 number = {5}
}

Spontaneous neuronal activity is spatiotemporally structured, influencing brain computations. Nevertheless, the neuronal interactions underlying these spontaneous activity patterns, and their biological relevance, remain elusive. Here, we addressed these questions using two-photon calcium imaging of intact zebrafish larvae to monitor the neuron-to-neuron spontaneous activity fine structure in the tectum, a region involved in visual spatial detection. Spontaneous activity was organized in topographically compact assemblies, grouping functionally similar neurons rather than merely neighboring ones, reflecting the tectal retinotopic map despite being independent of retinal drive. Assemblies represent all-or-none-like sub-networks shaped by competitive dynamics, mechanisms advantageous for visual detection in noisy natural environments. Notably, assemblies were tuned to the same angular sizes and spatial positions as prey-detection performance in behavioral assays, and their spontaneous activation predicted directional tail movements. Therefore, structured spontaneous activity represents "preferred" network states, tuned to behaviorally relevant features, emerging from the circuit's intrinsic non-linear dynamics, adapted for its functional role.

@article{
 title = {The world according to zebrafish: How neural circuits generate behavior},
 type = {article},
 year = {2014},
 keywords = {Behavior,Models of human brain disorders,Neuroanatomy,Neuronal circuit dynamics,Zebrafish},
 pages = {91},
 volume = {8},
 websites = {http://journal.frontiersin.org/article/10.3389/fncir.2014.00091/abstract},
 month = {7},
 publisher = {Frontiers},
 day = {30},
 id = {ffb8c6a4-a725-3196-a405-503287ae67ec},
 created = {2018-09-06T20:22:11.019Z},
 accessed = {2018-09-06},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2021-10-27T21:24:51.267Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Sumbre2014},
 private_publication = {false},
 abstract = {Understanding how the brain functions is one of the most ambitious current scientific goals. This challenge will only be accomplish by a multidisciplinary approach involving genetics, molecular biology, optics, ethology, neurobiology and mathematics and using tractable model systems. The zebrafish larva is a transparent genetically tractable small vertebrate, ideal for the combination state-of-the- art imaging techniques (e.g. two-photon scanning microscopy, single-plane illumination microscopy, spatial light modulator microscopy and lightfield microscopy), bioluminiscence and optogenetics to monitor and manipulate neuronal activity from single specific neurons up to the entire brain, in an intact behaving organism. Furthermore, the zebrafish model offers large and increasing collection of mutant and transgenic lines modelling human brain diseases. With these advantages in hand, the zebrafish larva became in the recent years, a novel animal model to study neuronal circuits and behaviour, taking us closer than ever before to understand how the brain controls behaviour.},
 bibtype = {article},
 author = {Sumbre, Germán and de Polavieja, Gonzalo G.},
 doi = {10.3389/fncir.2014.00091},
 journal = {Frontiers in Neural Circuits},
 number = {JULY}
}

Understanding how the brain functions is one of the most ambitious current scientific goals. This challenge will only be accomplish by a multidisciplinary approach involving genetics, molecular biology, optics, ethology, neurobiology and mathematics and using tractable model systems. The zebrafish larva is a transparent genetically tractable small vertebrate, ideal for the combination state-of-the- art imaging techniques (e.g. two-photon scanning microscopy, single-plane illumination microscopy, spatial light modulator microscopy and lightfield microscopy), bioluminiscence and optogenetics to monitor and manipulate neuronal activity from single specific neurons up to the entire brain, in an intact behaving organism. Furthermore, the zebrafish model offers large and increasing collection of mutant and transgenic lines modelling human brain diseases. With these advantages in hand, the zebrafish larva became in the recent years, a novel animal model to study neuronal circuits and behaviour, taking us closer than ever before to understand how the brain controls behaviour.

@article{
 title = {Monitoring tectal neuronal activities and motor behavior in zebrafish larvae.},
 type = {article},
 year = {2013},
 pages = {873-9},
 volume = {2013},
 websites = {http://www.cshprotocols.org/cgi/doi/10.1101/pdb.prot077131},
 month = {9},
 day = {1},
 id = {818187d0-6c7f-3d3a-af9f-feb9561ddda6},
 created = {2014-02-26T11:03:18.000Z},
 accessed = {2014-02-26},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2018-06-12T14:16:25.616Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Sumbre2013},
 private_publication = {false},
 abstract = {To understand how visuomotor behaviors are controlled by the nervous system, it is necessary to monitor the activity of large populations of neurons with single-cell resolution over a large area of the brain in a relatively simple, behaving organism. The zebrafish larva, a small lower vertebrate with transparent skin, serves as an excellent model for this purpose. Immediately after the larva hatches, it needs to catch prey and avoid predators. This strong evolutionary pressure leads to the rapid development of functional sensory systems, particularly vision. By 5 d postfertilization (dpf), tectal cells show distinct visually evoked patterns of activation, and the larvae are able to perform a variety of visuomotor behaviors. During the early larval stage, zebrafish breathe mainly through the skin and can be restrained under the microscope using a drop of low-melting-point agarose, without the use of anesthetics. Moreover, the transparency of the skin, the small diameter of the neurons (4-5 µm), and the high-neuronal density enable the use of in vivo noninvasive imaging techniques to monitor neuronal activities of up to ∼500 cells within the central nervous system, still with single-cell resolution. This article describes a method for simultaneously monitoring spontaneous and visually evoked activities of large populations of neurons in the optic tectum of the zebrafish larva, using a synthetic calcium dye (Oregon Green BAPTA-1 AM) and a conventional confocal or two-photon scanning fluorescence microscope, together with a method for measuring the tail motor behavior of the head-immobilized zebrafish larva.},
 bibtype = {article},
 author = {Sumbre, Germán and Poo, Mu-Ming},
 doi = {10.1101/pdb.prot077131},
 journal = {Cold Spring Harbor protocols},
 number = {9}
}

To understand how visuomotor behaviors are controlled by the nervous system, it is necessary to monitor the activity of large populations of neurons with single-cell resolution over a large area of the brain in a relatively simple, behaving organism. The zebrafish larva, a small lower vertebrate with transparent skin, serves as an excellent model for this purpose. Immediately after the larva hatches, it needs to catch prey and avoid predators. This strong evolutionary pressure leads to the rapid development of functional sensory systems, particularly vision. By 5 d postfertilization (dpf), tectal cells show distinct visually evoked patterns of activation, and the larvae are able to perform a variety of visuomotor behaviors. During the early larval stage, zebrafish breathe mainly through the skin and can be restrained under the microscope using a drop of low-melting-point agarose, without the use of anesthetics. Moreover, the transparency of the skin, the small diameter of the neurons (4-5 µm), and the high-neuronal density enable the use of in vivo noninvasive imaging techniques to monitor neuronal activities of up to ∼500 cells within the central nervous system, still with single-cell resolution. This article describes a method for simultaneously monitoring spontaneous and visually evoked activities of large populations of neurons in the optic tectum of the zebrafish larva, using a synthetic calcium dye (Oregon Green BAPTA-1 AM) and a conventional confocal or two-photon scanning fluorescence microscope, together with a method for measuring the tail motor behavior of the head-immobilized zebrafish larva.

@article{
 title = {The first mecp2-null zebrafish model shows altered motor behaviors},
 type = {article},
 year = {2013},
 keywords = {behaviour,mecp2,rett syndrome,zebrafish},
 pages = {118},
 volume = {7},
 websites = {http://journal.frontiersin.org/article/10.3389/fncir.2013.00118/abstract},
 id = {641042f4-a5fa-385d-841a-b932ec78ca81},
 created = {2018-06-12T14:21:54.326Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2020-01-08T13:02:45.215Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Pietri2013},
 private_publication = {false},
 abstract = {Rett syndrome (RTT) is an X-linked neurodevelopmental disorder and one of the most common causes of mental retardation in affected girls. Other symptoms include a rapid regression of motor and cognitive skills after an apparently early normal development. Sporadic mutations in the transcription factor MECP2 has been shown to be present in more than 90% of the patients and several models of MeCP2-deficient mice have been created to understand the role of this gene. These models have pointed toward alterations in the maintenance of the central nervous system rather than its development, in line with the late onset of the disease in humans. However, the exact functions of MeCP2 remain difficult to delineate and the animal models have yielded contradictory results. Here, we present the first mecp2-null allele mutation zebrafish model. Surprisingly and in contrast to MeCP2-null mouse models, mecp2-null zebrafish are viable and fertile. They present nonetheless clear behavioral alterations during their early development, including spontaneous and sensory-evoked motor anomalies, as well as defective thigmotaxis.},
 bibtype = {article},
 author = {Pietri, Thomas and Roman, Angel-Carlos and Guyon, Nicolas and Romano, Sebastián A and Washbourne, Philip and Moens, Cecilia B. and de Polavieja, Gonzalo G. and Sumbre, Germán},
 doi = {10.3389/fncir.2013.00118},
 journal = {Frontiers in Neural Circuits},
 number = {July}
}

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder and one of the most common causes of mental retardation in affected girls. Other symptoms include a rapid regression of motor and cognitive skills after an apparently early normal development. Sporadic mutations in the transcription factor MECP2 has been shown to be present in more than 90% of the patients and several models of MeCP2-deficient mice have been created to understand the role of this gene. These models have pointed toward alterations in the maintenance of the central nervous system rather than its development, in line with the late onset of the disease in humans. However, the exact functions of MeCP2 remain difficult to delineate and the animal models have yielded contradictory results. Here, we present the first mecp2-null allele mutation zebrafish model. Surprisingly and in contrast to MeCP2-null mouse models, mecp2-null zebrafish are viable and fertile. They present nonetheless clear behavioral alterations during their early development, including spontaneous and sensory-evoked motor anomalies, as well as defective thigmotaxis.

@article{
 title = {Fast functional imaging of multiple brain regions in intact zebrafish larvae using selective plane illumination microscopy.},
 type = {article},
 year = {2013},
 keywords = {correlation analysis,imaging,light-sheet imaging,neuroimaging,spontaneous activity,three-dimensional,zebrafish model system},
 pages = {65},
 volume = {7},
 websites = {http://journal.frontiersin.org/article/10.3389/fncir.2013.00065/abstract},
 month = {4},
 publisher = {Frontiers},
 day = {9},
 id = {f8c62ee5-cb3b-3119-b4b3-4f3ad79f958e},
 created = {2018-09-06T20:19:24.160Z},
 accessed = {2018-09-06},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2022-01-10T15:01:40.099Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Panier2013a},
 private_publication = {false},
 abstract = {The optical transparency and the small dimensions of zebrafish at the larval stage make it a vertebrate model of choice for brain-wide in-vivo functional imaging. However, current point-scanning imaging techniques, such as two-photon or confocal microscopy, impose a strong limit on acquisition speed which in turn sets the number of neurons that can be simultaneously recorded. At 5 Hz, this number is of the order of one thousand, i.e., approximately 1-2% of the brain. Here we demonstrate that this limitation can be greatly overcome by using Selective-plane Illumination Microscopy (SPIM). Zebrafish larvae expressing the genetically encoded calcium indicator GCaMP3 were illuminated with a scanned laser sheet and imaged with a camera whose optical axis was oriented orthogonally to the illumination plane. This optical sectioning approach was shown to permit functional imaging of a very large fraction of the brain volume of 5-9-day-old larvae with single- or near single-cell resolution. The spontaneous activity of up to 5,000 neurons was recorded at 20 Hz for 20-60 min. By rapidly scanning the specimen in the axial direction, the activity of 25,000 individual neurons from 5 different z-planes (approximately 30% of the entire brain) could be simultaneously monitored at 4 Hz. Compared to point-scanning techniques, this imaging strategy thus yields a ≃20-fold increase in data throughput (number of recorded neurons times acquisition rate) without compromising the signal-to-noise ratio (SNR). The extended field of view offered by the SPIM method allowed us to directly identify large scale ensembles of neurons, spanning several brain regions, that displayed correlated activity and were thus likely to participate in common neural processes. The benefits and limitations of SPIM for functional imaging in zebrafish as well as future developments are briefly discussed.},
 bibtype = {article},
 author = {Panier, Thomas and Romano, Sebastián A. and Olive, Raphaël and Pietri, Thomas and Sumbre, Germán and Candelier, Raphaël and Debrégeas, Georges},
 doi = {10.3389/fncir.2013.00065},
 journal = {Frontiers in neural circuits}
}

The optical transparency and the small dimensions of zebrafish at the larval stage make it a vertebrate model of choice for brain-wide in-vivo functional imaging. However, current point-scanning imaging techniques, such as two-photon or confocal microscopy, impose a strong limit on acquisition speed which in turn sets the number of neurons that can be simultaneously recorded. At 5 Hz, this number is of the order of one thousand, i.e., approximately 1-2% of the brain. Here we demonstrate that this limitation can be greatly overcome by using Selective-plane Illumination Microscopy (SPIM). Zebrafish larvae expressing the genetically encoded calcium indicator GCaMP3 were illuminated with a scanned laser sheet and imaged with a camera whose optical axis was oriented orthogonally to the illumination plane. This optical sectioning approach was shown to permit functional imaging of a very large fraction of the brain volume of 5-9-day-old larvae with single- or near single-cell resolution. The spontaneous activity of up to 5,000 neurons was recorded at 20 Hz for 20-60 min. By rapidly scanning the specimen in the axial direction, the activity of 25,000 individual neurons from 5 different z-planes (approximately 30% of the entire brain) could be simultaneously monitored at 4 Hz. Compared to point-scanning techniques, this imaging strategy thus yields a ≃20-fold increase in data throughput (number of recorded neurons times acquisition rate) without compromising the signal-to-noise ratio (SNR). The extended field of view offered by the SPIM method allowed us to directly identify large scale ensembles of neurons, spanning several brain regions, that displayed correlated activity and were thus likely to participate in common neural processes. The benefits and limitations of SPIM for functional imaging in zebrafish as well as future developments are briefly discussed.

@article{
 title = {Region-Specific Contribution of Ephrin-B and Wnt Signaling to Receptive Field Plasticity in Developing Optic Tectum},
 type = {article},
 year = {2010},
 keywords = {Action Potentials,Action Potentials: genetics,Animals,Ephrin-B1,Ephrin-B1: biosynthesis,Ephrin-B1: genetics,Ephrin-B1: physiology,Genetically Modified,Molneuro,Neuronal Plasticity,Neuronal Plasticity: physiology,Photic Stimulation,Photic Stimulation: methods,Retinal Ganglion Cells,Retinal Ganglion Cells: metabolism,Signal Transduction,Signal Transduction: genetics,Signaling,Superior Colliculi,Superior Colliculi: growth & development,Superior Colliculi: metabolism,Visual Fields,Visual Fields: physiology,Visual Pathways,Visual Pathways: growth & development,Visual Pathways: metabolism,Wnt Proteins,Wnt Proteins: biosynthesis,Wnt Proteins: genetics,Wnt Proteins: physiology,Wnt3 Protein,Xenopus laevis},
 pages = {899-911},
 volume = {65},
 websites = {http://linkinghub.elsevier.com/retrieve/pii/S0896627310001790},
 month = {3},
 publisher = {Elsevier Ltd},
 day = {25},
 id = {8f116e51-6aaa-3276-8113-43fd764182bc},
 created = {2018-05-30T15:32:51.918Z},
 accessed = {2014-02-26},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2018-06-21T12:44:38.342Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Lim2010},
 private_publication = {false},
 abstract = {Ephrin-B/EphB and Wnts are known to regulate synapse maturation and plasticity, besides serving as axon guidance molecules, but the relevance of such synaptic regulation to neural circuit functions in vivo remains unclear. In this study, we have examined the role of ephrin-B and Wnt signaling in regulating visual experience-dependent and developmental plasticity of receptive fields (RFs) of tectal cells in the developing Xenopus optic tectum. We found that repetitive exposure to unidirectional moving visual stimuli caused varying degrees of shift in the RFs in different regions of the tectum. By acute perfusion of exogenous antagonists and inducible transgene expression, we showed that ephrin-B signaling in presynaptic retinal ganglion cells and Wnt secretion from tectal cells are specifically responsible for the enhanced visual stimulation-induced changes in neuronal responses and RFs in the ventral and dorsal tectum, respectively. Thus, ephrin-B and Wnt signaling contribute to region-specific plasticity of visual circuit functions. © 2010 Elsevier Inc.},
 bibtype = {article},
 author = {Lim, Byung Kook and Cho, Sung-jin jin and Sumbre, German and Poo, Mu-ming ming},
 doi = {10.1016/j.neuron.2010.03.008},
 journal = {Neuron},
 number = {6}
}

Ephrin-B/EphB and Wnts are known to regulate synapse maturation and plasticity, besides serving as axon guidance molecules, but the relevance of such synaptic regulation to neural circuit functions in vivo remains unclear. In this study, we have examined the role of ephrin-B and Wnt signaling in regulating visual experience-dependent and developmental plasticity of receptive fields (RFs) of tectal cells in the developing Xenopus optic tectum. We found that repetitive exposure to unidirectional moving visual stimuli caused varying degrees of shift in the RFs in different regions of the tectum. By acute perfusion of exogenous antagonists and inducible transgene expression, we showed that ephrin-B signaling in presynaptic retinal ganglion cells and Wnt secretion from tectal cells are specifically responsible for the enhanced visual stimulation-induced changes in neuronal responses and RFs in the ventral and dorsal tectum, respectively. Thus, ephrin-B and Wnt signaling contribute to region-specific plasticity of visual circuit functions. © 2010 Elsevier Inc.

@article{
 title = {Nonsomatotopic Organization of the Higher Motor Centers in Octopus},
 type = {article},
 year = {2009},
 keywords = {SYSNEURO},
 pages = {1632-1636},
 volume = {19},
 websites = {http://linkinghub.elsevier.com/retrieve/pii/S0960982209015462},
 month = {10},
 publisher = {Elsevier Ltd},
 id = {f9648441-8a3e-3987-a92b-2d39d7c38522},
 created = {2018-05-30T14:04:03.672Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2018-06-21T12:44:38.489Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Zullo2009a},
 private_publication = {false},
 abstract = {Hyperredundant limbs with a virtually unlimited number of degrees of freedom (DOFs) pose a challenge for both biological and computational systems of motor control. In the flexible arms of the octopus, simplification strategies have evolved to reduce the number of controlled DOFs [1-3]. Motor control in the octopus nervous system is hierarchically organized [4, 5]. A relatively small central brain integrates a huge amount of visual and tactile information from the large optic lobes and the peripheral nervous system of the arms [6-9] and issues commands to lower motor centers controlling the elaborated neuromuscular system of the arms. This unique organization raises new questions on the organization of the octopus brain and whether and how it represents the rich movement repertoire. We developed a method of brain microstimulation in freely behaving animals and stimulated the higher motor centers-the basal lobes-thus inducing discrete and complex sets of movements. As stimulation strength increased, complex movements were recruited from basic components shared by different types of movement. We found no stimulation site where movements of a single arm or body part could be elicited. Discrete and complex components have no central topographical organization but are distributed over wide regions. © 2009 Elsevier Ltd. All rights reserved.},
 bibtype = {article},
 author = {Zullo, Letizia and Sumbre, German and Agnisola, Claudio and Flash, Tamar and Hochner, Binyamin},
 doi = {10.1016/j.cub.2009.07.067},
 journal = {Current Biology},
 number = {19}
}

Hyperredundant limbs with a virtually unlimited number of degrees of freedom (DOFs) pose a challenge for both biological and computational systems of motor control. In the flexible arms of the octopus, simplification strategies have evolved to reduce the number of controlled DOFs [1-3]. Motor control in the octopus nervous system is hierarchically organized [4, 5]. A relatively small central brain integrates a huge amount of visual and tactile information from the large optic lobes and the peripheral nervous system of the arms [6-9] and issues commands to lower motor centers controlling the elaborated neuromuscular system of the arms. This unique organization raises new questions on the organization of the octopus brain and whether and how it represents the rich movement repertoire. We developed a method of brain microstimulation in freely behaving animals and stimulated the higher motor centers-the basal lobes-thus inducing discrete and complex sets of movements. As stimulation strength increased, complex movements were recruited from basic components shared by different types of movement. We found no stimulation site where movements of a single arm or body part could be elicited. Discrete and complex components have no central topographical organization but are distributed over wide regions. © 2009 Elsevier Ltd. All rights reserved.

@article{
 title = {Entrained rhythmic activities of neuronal ensembles as perceptual memory of time interval.},
 type = {article},
 year = {2008},
 pages = {102-6},
 volume = {456},
 websites = {http://www.nature.com/doifinder/10.1038/nature07351},
 month = {11},
 day = {6},
 id = {e587876b-bbda-3c83-bea6-47af7b90cb81},
 created = {2014-04-16T08:37:52.000Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2018-06-12T14:16:25.550Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Sumbre2008},
 private_publication = {false},
 abstract = {The ability to process temporal information is fundamental to sensory perception, cognitive processing and motor behaviour of all living organisms, from amoebae to humans. Neural circuit mechanisms based on neuronal and synaptic properties have been shown to process temporal information over the range of tens of microseconds to hundreds of milliseconds. How neural circuits process temporal information in the range of seconds to minutes is much less understood. Studies of working memory in monkeys and rats have shown that neurons in the prefrontal cortex, the parietal cortex and the thalamus exhibit ramping activities that linearly correlate with the lapse of time until the end of a specific time interval of several seconds that the animal is trained to memorize. Many organisms can also memorize the time interval of rhythmic sensory stimuli in the timescale of seconds and can coordinate motor behaviour accordingly, for example, by keeping the rhythm after exposure to the beat of music. Here we report a form of rhythmic activity among specific neuronal ensembles in the zebrafish optic tectum, which retains the memory of the time interval (in the order of seconds) of repetitive sensory stimuli for a duration of up to approximately 20 s. After repetitive visual conditioning stimulation (CS) of zebrafish larvae, we observed rhythmic post-CS activities among specific tectal neuronal ensembles, with a regular interval that closely matched the CS. Visuomotor behaviour of the zebrafish larvae also showed regular post-CS repetitions at the entrained time interval that correlated with rhythmic neuronal ensemble activities in the tectum. Thus, rhythmic activities among specific neuronal ensembles may act as an adjustable 'metronome' for time intervals in the order of seconds, and serve as a mechanism for the short-term perceptual memory of rhythmic sensory experience.},
 bibtype = {article},
 author = {Sumbre, Germán and Muto, Akira and Baier, Herwig and Poo, Mu-ming},
 doi = {10.1038/nature07351},
 journal = {Nature},
 number = {7218}
}

The ability to process temporal information is fundamental to sensory perception, cognitive processing and motor behaviour of all living organisms, from amoebae to humans. Neural circuit mechanisms based on neuronal and synaptic properties have been shown to process temporal information over the range of tens of microseconds to hundreds of milliseconds. How neural circuits process temporal information in the range of seconds to minutes is much less understood. Studies of working memory in monkeys and rats have shown that neurons in the prefrontal cortex, the parietal cortex and the thalamus exhibit ramping activities that linearly correlate with the lapse of time until the end of a specific time interval of several seconds that the animal is trained to memorize. Many organisms can also memorize the time interval of rhythmic sensory stimuli in the timescale of seconds and can coordinate motor behaviour accordingly, for example, by keeping the rhythm after exposure to the beat of music. Here we report a form of rhythmic activity among specific neuronal ensembles in the zebrafish optic tectum, which retains the memory of the time interval (in the order of seconds) of repetitive sensory stimuli for a duration of up to approximately 20 s. After repetitive visual conditioning stimulation (CS) of zebrafish larvae, we observed rhythmic post-CS activities among specific tectal neuronal ensembles, with a regular interval that closely matched the CS. Visuomotor behaviour of the zebrafish larvae also showed regular post-CS repetitions at the entrained time interval that correlated with rhythmic neuronal ensemble activities in the tectum. Thus, rhythmic activities among specific neuronal ensembles may act as an adjustable 'metronome' for time intervals in the order of seconds, and serve as a mechanism for the short-term perceptual memory of rhythmic sensory experience.

@article{
 title = {LKB1/STRAD Promotes Axon Initiation During Neuronal Polarization},
 type = {article},
 year = {2007},
 keywords = {Animals,Axons,Axons: metabolism,Brain-Derived Neurotrophic Factor,Brain-Derived Neurotrophic Factor: metabolism,Carrier Proteins,Carrier Proteins: metabolism,Cell Line,Cell Polarity,Cyclic AMP,Cyclic AMP-Dependent Protein Kinases,Cyclic AMP-Dependent Protein Kinases: metabolism,Cyclic AMP: metabolism,Down-Regulation,Embryo,Humans,MOLNEURO,Mammalian,Mammalian: cytology,Neurites,Neurites: metabolism,Neurons,Neurons: cytology,Neurons: metabolism,Phosphorylation,Protein-Serine-Threonine Kinases,Protein-Serine-Threonine Kinases: metabolism,Rats,Signal Transduction},
 pages = {565-577},
 volume = {129},
 websites = {http://linkinghub.elsevier.com/retrieve/pii/S0092867407004692},
 month = {5},
 day = {4},
 id = {9dea7352-e8eb-308e-b483-79e056687488},
 created = {2012-08-02T15:18:31.000Z},
 accessed = {2012-07-21},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2018-06-12T14:15:46.264Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Shelly2007},
 private_publication = {false},
 abstract = {Axon/dendrite differentiation is a critical step in neuronal development. In cultured hippocampal neurons, the accumulation of LKB1 and STRAD, two interacting proteins critical for establishing epithelial polarity, in an undifferentiated neurite correlates with its subsequent axon differentiation. Downregulation of either LKB1 or STRAD by siRNAs prevented axon differentiation, and overexpression of these proteins led to multiple axon formation. Furthermore, interaction of STRAD with LKB1 promoted LKB1 phosphorylation at a PKA site S431 and elevated the LKB1 level, and overexpressing LKB1 with a serine-to-alanine mutation at S431 (LKB1(S431A)) prevented axon differentiation. In developing cortical neurons in vivo, downregulation of LKB1 or overexpression of LKB1(S431A) also abolished axon formation. Finally, local exposure of the undifferentiated neurite to brain-derived neurotrophic factor or dibutyryl-cAMP promoted axon differentiation in a manner that depended on PKA-dependent LKB1 phosphorylation. Thus local LKB1/STRAD accumulation and PKA-dependent LKB1 phosphorylation represents an early signal for axon initiation.},
 bibtype = {article},
 author = {Shelly, Maya and Cancedda, Laura and Heilshorn, Sarah and Sumbre, Germán and Poo, Mu-ming},
 doi = {10.1016/j.cell.2007.04.012},
 journal = {Cell},
 number = {3}
}

Axon/dendrite differentiation is a critical step in neuronal development. In cultured hippocampal neurons, the accumulation of LKB1 and STRAD, two interacting proteins critical for establishing epithelial polarity, in an undifferentiated neurite correlates with its subsequent axon differentiation. Downregulation of either LKB1 or STRAD by siRNAs prevented axon differentiation, and overexpression of these proteins led to multiple axon formation. Furthermore, interaction of STRAD with LKB1 promoted LKB1 phosphorylation at a PKA site S431 and elevated the LKB1 level, and overexpressing LKB1 with a serine-to-alanine mutation at S431 (LKB1(S431A)) prevented axon differentiation. In developing cortical neurons in vivo, downregulation of LKB1 or overexpression of LKB1(S431A) also abolished axon formation. Finally, local exposure of the undifferentiated neurite to brain-derived neurotrophic factor or dibutyryl-cAMP promoted axon differentiation in a manner that depended on PKA-dependent LKB1 phosphorylation. Thus local LKB1/STRAD accumulation and PKA-dependent LKB1 phosphorylation represents an early signal for axon initiation.

@article{
 title = {Octopuses Use a Human-like Strategy to Control Precise Point-to-Point Arm Movements},
 type = {article},
 year = {2006},
 keywords = {SYSNEURO},
 pages = {767-772},
 volume = {16},
 websites = {http://linkinghub.elsevier.com/retrieve/pii/S0960982206012747},
 month = {4},
 day = {18},
 id = {7c920eac-ef43-3bad-82a8-4cc6975c6302},
 created = {2018-05-30T14:04:03.779Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2018-06-21T12:44:38.236Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Sumbre2006},
 private_publication = {false},
 abstract = {One of the key problems in motor control is mastering or reducing the number of degrees of freedom (DOFs) through coordination. This problem is especially prominent with hyper-redundant limbs such as the extremely flexible arm of the octopus. Several strategies for simplifying these control problems have been suggested for human point-to-point arm movements. Despite the evolutionary gap and morphological differences, humans and octopuses evolved similar strategies when fetching food to the mouth. To achieve this precise point-to-point-task, octopus arms generate a quasi-articulated structure based on three dynamic joints. A rotational movement around these joints brings the object to the mouth . Here, we describe a peripheral neural mechanism-two waves of muscle activation propagate toward each other, and their collision point sets the medial-joint location. This is a remarkably simple mechanism for adjusting the length of the segments according to where the object is grasped. Furthermore, similar to certain human arm movements, kinematic invariants were observed at the joint level rather than at the end-effector level, suggesting intrinsic control coordination. The evolutionary convergence to similar geometrical and kinematic features suggests that a kinematically constrained articulated limb controlled at the level of joint space is the optimal solution for precise point-to-point movements.},
 bibtype = {article},
 author = {Sumbre, Germán and Fiorito, Graziano and Flash, Tamar and Hochner, Binyamin},
 doi = {10.1016/j.cub.2006.02.069},
 journal = {Current Biology},
 number = {8}
}

One of the key problems in motor control is mastering or reducing the number of degrees of freedom (DOFs) through coordination. This problem is especially prominent with hyper-redundant limbs such as the extremely flexible arm of the octopus. Several strategies for simplifying these control problems have been suggested for human point-to-point arm movements. Despite the evolutionary gap and morphological differences, humans and octopuses evolved similar strategies when fetching food to the mouth. To achieve this precise point-to-point-task, octopus arms generate a quasi-articulated structure based on three dynamic joints. A rotational movement around these joints brings the object to the mouth . Here, we describe a peripheral neural mechanism-two waves of muscle activation propagate toward each other, and their collision point sets the medial-joint location. This is a remarkably simple mechanism for adjusting the length of the segments according to where the object is grasped. Furthermore, similar to certain human arm movements, kinematic invariants were observed at the joint level rather than at the end-effector level, suggesting intrinsic control coordination. The evolutionary convergence to similar geometrical and kinematic features suggests that a kinematically constrained articulated limb controlled at the level of joint space is the optimal solution for precise point-to-point movements.

@article{
 title = {Neurobiology: motor control of flexible octopus arms.},
 type = {article},
 year = {2005},
 pages = {595-6},
 volume = {433},
 websites = {http://www.nature.com/doifinder/10.1038/433595a},
 month = {2},
 day = {10},
 id = {d5193390-0e7b-3281-8682-327d7450357e},
 created = {2014-04-04T12:47:23.000Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2019-03-14T09:39:39.995Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Sumbre2005},
 private_publication = {false},
 abstract = {Animals with rigid skeletons can rely on several mechanisms to simplify motor control--for example, they have skeletal joints that reduce the number of variables and degrees of freedom that need to be controlled. Here we show that when the octopus uses one of its long and highly flexible arms to transfer an object from one place to another, it employs a vertebrate-like strategy, temporarily reconfiguring its arm into a stiffened, articulated, quasi-jointed structure. This indicates that an articulated limb may provide an optimal solution for achieving precise, point-to-point movements.},
 bibtype = {article},
 author = {Sumbre, Germán and Fiorito, Graziano and Flash, Tamar and Hochner, Binyamin},
 doi = {10.1038/433595a},
 journal = {Nature},
 number = {7026}
}

Animals with rigid skeletons can rely on several mechanisms to simplify motor control--for example, they have skeletal joints that reduce the number of variables and degrees of freedom that need to be controlled. Here we show that when the octopus uses one of its long and highly flexible arms to transfer an object from one place to another, it employs a vertebrate-like strategy, temporarily reconfiguring its arm into a stiffened, articulated, quasi-jointed structure. This indicates that an articulated limb may provide an optimal solution for achieving precise, point-to-point movements.

@article{
 title = {How to move with no rigid skeleton? The octopus has the answers.},
 type = {article},
 year = {2002},
 keywords = {Animals,Extremities,Extremities: physiology,Movement,Movement: physiology,Octopodiformes,Octopodiformes: anatomy & histology,Octopodiformes: physiology,Psychomotor Performance,Psychomotor Performance: physiology},
 pages = {250-4},
 volume = {49},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/12486300},
 month = {12},
 id = {05166f8f-5d78-3854-be67-971571e53721},
 created = {2012-08-16T12:24:30.000Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2018-06-12T14:15:46.002Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Yekutieli2002},
 private_publication = {false},
 abstract = {The octopus is amazingly flexible and shows exceptional control and coordination in all its movements. It seems remarkable to us skeletal creatures that the octopus achieves all this without a single bone.},
 bibtype = {article},
 author = {Yekutieli, Yoram and Sumbre, German and Flash, Tamar and Hochner, Binyamin},
 journal = {Biologist},
 number = {6}
}

The octopus is amazingly flexible and shows exceptional control and coordination in all its movements. It seems remarkable to us skeletal creatures that the octopus achieves all this without a single bone.

@article{
 title = {Control of octopus arm extension by a peripheral motor program.},
 type = {article},
 year = {2001},
 keywords = {Animals,Electric Stimulation,Electromyography,Motor Neurons,Motor Neurons: physiology,Movement,Movement: physiology,Muscle Denervation,Nerve Net,Nerve Net: physiology,Octopodiformes,Octopodiformes: physiology,Peripheral Nervous System,Peripheral Nervous System: physiology},
 pages = {1845-8},
 volume = {293},
 websites = {http://www.sciencemag.org/cgi/doi/10.1126/science.1060976},
 month = {9},
 day = {7},
 id = {d56e5b57-792c-3429-aa4f-6051a571c4a1},
 created = {2012-08-16T12:24:36.000Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2018-06-12T14:16:25.618Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Sumbre2001},
 private_publication = {false},
 abstract = {For goal-directed arm movements, the nervous system generates a sequence of motor commands that bring the arm toward the target. Control of the octopus arm is especially complex because the arm can be moved in any direction, with a virtually infinite number of degrees of freedom. Here we show that arm extensions can be evoked mechanically or electrically in arms whose connection with the brain has been severed. These extensions show kinematic features that are almost identical to normal behavior, suggesting that the basic motor program for voluntary movement is embedded within the neural circuitry of the arm itself. Such peripheral motor programs represent considerable simplification in the motor control of this highly redundant appendage.},
 bibtype = {article},
 author = {Sumbre, G and Gutfreund, Y and Fiorito, G and Flash, T and Hochner, B},
 doi = {10.1126/science.1060976},
 journal = {Science},
 number = {5536}
}

For goal-directed arm movements, the nervous system generates a sequence of motor commands that bring the arm toward the target. Control of the octopus arm is especially complex because the arm can be moved in any direction, with a virtually infinite number of degrees of freedom. Here we show that arm extensions can be evoked mechanically or electrically in arms whose connection with the brain has been severed. These extensions show kinematic features that are almost identical to normal behavior, suggesting that the basic motor program for voluntary movement is embedded within the neural circuitry of the arm itself. Such peripheral motor programs represent considerable simplification in the motor control of this highly redundant appendage.

@article{
 title = {Wing-beat coupling between flying locust pairs: preferred phase and lift enhancement},
 type = {article},
 year = {1995},
 keywords = {insect flight,lift,locust,locusta,phase,wing-beat},
 pages = {1051-63},
 volume = {198},
 websites = {http://jeb.biologists.org/content/198/4/1051},
 month = {1},
 id = {4190ca6b-bb1e-35ee-9704-b36d6bbc753d},
 created = {2016-01-25T13:04:57.000Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2020-01-08T13:02:45.147Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Camhi1995},
 source_type = {article},
 private_publication = {false},
 abstract = {Pairs of locusts flying in tandem in a wind tunnel are known to couple their wing-beats intermittently. The rhythmically oscillating air flow from the front locust's wing-beat, detected by the rear individual, appears to convey the timing information for coupling. Three predictions of this arrangement were tested quantitatively in this study. (1) Given that the oscillating air flow has a wavelength of 7.5 cm, placing the rear locust 7.5 or 15 cm behind the front one should produce the same phase of coupling, whereas placing it at an intermediate distance of 11 cm should produce an opposite phase. (2) At any distance, the preferred phase at which wing-beat coupling occurs should depend, in part, on the difference in the wing-beat frequencies of the two locusts just before the coupling began. (3) At the moment that the wing-beats of the two locusts become coupled, a change should be observed consistently in the wing-beat frequency of the rear individual only. Each of these three predictions was fulfilled. We also recorded the instantaneous lift of the rear locust by tethering it to a laser torque meter. Lift varied with the phase of the wing-beats between the two locusts. For a given distance between the two locusts, lift was greater by a mean of 16 % of the locust's body mass at those phases where coupling most commonly occurred than at opposite phases. This lift effect was seen even if the wing-beats of the two locusts drifted through these preferred phases without actually coupling. These results are discussed in terms of a possible energetic advantage conferred to the rear locust by flying in tandem and by coupling its flight rhythm to the leader's wing-beat.},
 bibtype = {article},
 author = {Camhi, undefined and Sumbre, undefined and Wendler, undefined},
 journal = {The Journal of Experimental Biology},
 number = {Pt 4}
}

Pairs of locusts flying in tandem in a wind tunnel are known to couple their wing-beats intermittently. The rhythmically oscillating air flow from the front locust's wing-beat, detected by the rear individual, appears to convey the timing information for coupling. Three predictions of this arrangement were tested quantitatively in this study. (1) Given that the oscillating air flow has a wavelength of 7.5 cm, placing the rear locust 7.5 or 15 cm behind the front one should produce the same phase of coupling, whereas placing it at an intermediate distance of 11 cm should produce an opposite phase. (2) At any distance, the preferred phase at which wing-beat coupling occurs should depend, in part, on the difference in the wing-beat frequencies of the two locusts just before the coupling began. (3) At the moment that the wing-beats of the two locusts become coupled, a change should be observed consistently in the wing-beat frequency of the rear individual only. Each of these three predictions was fulfilled. We also recorded the instantaneous lift of the rear locust by tethering it to a laser torque meter. Lift varied with the phase of the wing-beats between the two locusts. For a given distance between the two locusts, lift was greater by a mean of 16 % of the locust's body mass at those phases where coupling most commonly occurred than at opposite phases. This lift effect was seen even if the wing-beats of the two locusts drifted through these preferred phases without actually coupling. These results are discussed in terms of a possible energetic advantage conferred to the rear locust by flying in tandem and by coupling its flight rhythm to the leader's wing-beat.

@article{
 title = {Close encounters among flying locusts produce wing-beat coupling},
 type = {article},
 year = {1994},
 keywords = {Animal,Animal: physiology,Animals,Cooperative Behavior,Female,Flight,Locusta migratoria,Locusta migratoria: physiology,Wing,Wing: physiology},
 pages = {643-649},
 volume = {174},
 websites = {http://link.springer.com/10.1007/BF00217385},
 month = {5},
 id = {e9935c10-ad77-3777-9e46-8d4378ab6472},
 created = {2012-08-16T12:24:29.000Z},
 file_attached = {true},
 profile_id = {91806a5d-0b39-358d-8731-94e154a41c8d},
 last_modified = {2020-01-08T13:02:45.154Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Kutsch1994},
 private_publication = {false},
 abstract = {Any flying animal leaves behind a wake of turbulent air. Thus, a closely tailing neighbor may be buffeted by complex aerodynamic forces. We report here that pairs of tethered locusts (Locusta migratoria) flying in tandem in a wind tunnel, couple their wing-beats to one another.Wind-receptive hairs on the rear partner's head provide the main sensory input that produces the coupling. The phase angle of coupling depends upon the distance between the individuals. By phase-coupling to a forward neighbor's wake, a locust may turn this turbulence to its own aerodynamic advantage. Moreover, within a large swarm local groups of locusts may fly in a functionally integrated manner.},
 bibtype = {article},
 author = {Kutsch, W and Camhi, J and Sumbre, G},
 doi = {10.1007/BF00217385},
 journal = {Journal of Comparative Physiology A},
 number = {5}
}

Any flying animal leaves behind a wake of turbulent air. Thus, a closely tailing neighbor may be buffeted by complex aerodynamic forces. We report here that pairs of tethered locusts (Locusta migratoria) flying in tandem in a wind tunnel, couple their wing-beats to one another.Wind-receptive hairs on the rear partner's head provide the main sensory input that produces the coupling. The phase angle of coupling depends upon the distance between the individuals. By phase-coupling to a forward neighbor's wake, a locust may turn this turbulence to its own aerodynamic advantage. Moreover, within a large swarm local groups of locusts may fly in a functionally integrated manner.