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

• Published in: Cell Vol. 167; no. 4; pp. 947 - 960.e20
• Main Authors: Naumann, Eva A., Fitzgerald, James E., Dunn, Timothy W., Rihel, Jason, Sompolinsky, Haim, Engert, Florian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.11.2016
• Subjects: Animals; behavioral analysis; brain; Brain - physiology; calcium imaging; circuit model; Danio rerio; Feedback, Sensory; image analysis; Neural Pathways; Neuroimaging; Neurons; neurophysiology; streams; Swimming; two-photon imaging; vertebrates; Visual Perception; zebrafish; Zebrafish - physiology; circuit model; behavioral analysis; two-photon imaging; zebrafish; calcium imaging
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2016.10.019

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. [Display omitted] •Optomotor response is driven asymmetrically by visual motion to each eye•Dedicated circuits differentially process eye- and direction-specific motion•Neural representations are distributed over select overrepresented response types•Behavior and neural activity are captured by realistic whole-brain circuit model Whole-brain imaging and behavioral analysis combined with network modeling reveal key circuit elements contributing to a complex sensorimotor behavior in zebrafish larvae and provide a framework for building brain-level circuit models.