Predicting modular functions and neural coding of behavior from a synaptic wiring diagram

Abstract

A long-standing goal in neuroscience is to understand how a circuit’s form influences its function. Here, we reconstruct and analyze a synaptic wiring diagram of the larval zebrafish brainstem to predict key functional properties and validate them through comparison with physiological data. We identify modules of strongly connected neurons that turn out to be specialized for different behavioral functions, the control of eye and body movements. The eye movement module is further organized into two three-block cycles that support the positive feedback long hypothesized to underlie low-dimensional attractor dynamics in oculomotor control. We construct a neural network model based directly on the reconstructed wiring diagram that makes predictions for the cellular-resolution coding of eye position and neural dynamics. These predictions are verified statistically with calcium imaging-based neural activity recordings. This work demonstrates how connectome-based brain modeling can reveal previously unknown anatomical structure in a neural circuit and provide insights linking network form to function.