# Sensorimotor processing, decision making, and internal states: towards a realistic multiscale circuit model of the larval zebrafish brain

> **NIH NIH U19** · HARVARD UNIVERSITY · 2021 · $3,629,683

## Abstract

Project Summary - A realistic multiscale circuit model of the larval zebrafish brain
The working group of the BRAIN initiative (BRAIN 2025, a Scientific Vision) identified “the analysis of circuits of
interacting neurons as being particularly rich in opportunity, with potential for revolutionary advances”. They further
pointed out that “truly understanding a circuit requires identifying and characterizing the component cells, defining their
synaptic connections with one another, observing their dynamic patterns of activity as their circuit functions in vivo
during behavior, and perturbing these patterns to test their significance. It also requires an understanding of the algorithms
that govern information processing within a circuit and between interacting circuits in the brain as a whole”.
We propose to generate a realistic multiscale circuit model of the larval zebrafish brain – the multiscale virtual fish
(MVF), which is well aligned with the BRAIN initiative's guidelines. 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 optogenetic interrogation and sparse connectomics of identified circuit
elements 1​ ,2​. The ultimate purpose is to explain and simulate the quantitative and qualitative nature of behavioral outputs
in response to sensory inputs across various timescales, and to explore how these findings might integrate with parallel
work in two other important behavioral model systems, ​ the ​Drosophila larva and the rat.
Our prior U01 project achieved the first instantiation of this model, whereby we successfully dissected the optomotor
response (OMR)1​ ​, where a larval zebrafish will turn and swim to match the direction of a whole-field visual stimulus ​3–5.​
We will build on this model by achieving three further aims: First, we will expand the OMR project with four additional
ethologically relevant behaviors: phototaxis, rheotaxis, escape, and hunting. We will extract the precise algorithms
underlying each behavior and develop a version of the circuit model to understand their neural implementation. Second,
we will further refine the model to account for multimodal integration and decision making, events that naturally happen
when conflicting stimuli driving different behaviors are presented simultaneously. For example, a fish might be driven to
execute a left turn by whole field motion moving to the left (OMR), while simultaneously being induced to turn right by
increased brightness on its right side (phototaxis). Third, we will examine how internal brain states, such as hunger or
stress, influence and modulate the specific behaviors (Aim 1) or behavioral interactions (Aim 2). Implementation of
neurochemical modulation into the framework of the MVF will ...

## Key facts

- **NIH application ID:** 10241477
- **Project number:** 5U19NS104653-05
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Florian Engert
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $3,629,683
- **Award type:** 5
- **Project period:** 2017-09-25 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241477

## Citation

> US National Institutes of Health, RePORTER application 10241477, Sensorimotor processing, decision making, and internal states: towards a realistic multiscale circuit model of the larval zebrafish brain (5U19NS104653-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10241477. Licensed CC0.

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