We present here a framework to generate a realistic multiscale circuit model of the larval zebrafish brain – the multiscale virtual fish (MVF). The model will be based on algorithms inferred from behavioral assays and it will span spatial ranges across three levels: from the nanoscale at the synaptic level, to the microscale describing local circuits, to the macroscale brain-wide activity patterns distributed across many regions. The model will be constrained and validated by functional imaging and sparse connectomics of identified circuit elements.

Specifically, we focus on five ethologically relevant behaviors: the opto-motor response, phototaxis, rheotaxis, escape, and hunting. First, we extract the precise algorithms underlying each behavior and develop a version of the circuit model to understand their neural implementation. Second, we refine the model to account for multimodal integration and decision making, events that naturally happen when conflicting stimuli driving different behaviors are presented simultaneously. Third, we will examine how internal brain states, such as hunger or stress, influence and modulate the specific behaviors or behavioral interactions. Implementation of neurochemical modulation into the framework of the MVF will be achieved through simulation of highly conserved neuromodulatory neurotransmitter systems such as serotonin, acetylcholine, epinephrine, dopamine and oxytocin.

Learning Objectives:

1. Describe the advantages (and disadvantages) of the larval zebrafish as a model system for Neuroscience.
2. Discuss what specific questions in neuroscience can be answered by combining brain wide recordings of neural activity with brain wide connectomics in the same animal.