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Cell. 2016 Nov 3;167(4):947-960.e20. doi: 10.1016/j.cell.2016.10.019.

From Whole-Brain Data to Functional Circuit Models: The Zebrafish Optomotor Response.

Author information

1
Department of Molecular & Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
2
Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
3
Department of Molecular & Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
4
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
5
Center for Brain Science, Harvard University, Cambridge, MA 02138, USA; Racah Institute of Physics and the Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
6
Department of Molecular & Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Center for Brain Science, Harvard University, Cambridge, MA 02138, USA. Electronic address: florian@mcb.harvard.edu.

Abstract

Detailed descriptions of brain-scale sensorimotor circuits underlying vertebrate behavior remain elusive. Recent advances in zebrafish neuroscience offer new opportunities to dissect such circuits via whole-brain imaging, behavioral analysis, functional perturbations, and network modeling. Here, we harness these tools to generate a brain-scale circuit model of the optomotor response, an orienting behavior evoked by visual motion. We show that such motion is processed by diverse neural response types distributed across multiple brain regions. To transform sensory input into action, these regions sequentially integrate eye- and direction-specific sensory streams, refine representations via interhemispheric inhibition, and demix locomotor instructions to independently drive turning and forward swimming. While experiments revealed many neural response types throughout the brain, modeling identified the dimensions of functional connectivity most critical for the behavior. We thus reveal how distributed neurons collaborate to generate behavior and illustrate a paradigm for distilling functional circuit models from whole-brain data.

KEYWORDS:

behavioral analysis; calcium imaging; circuit model; two-photon imaging; zebrafish

PMID:
27814522
PMCID:
PMC5111816
DOI:
10.1016/j.cell.2016.10.019
[Indexed for MEDLINE]
Free PMC Article

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