# Circadian regulation of brain and body in larval zebrafish

> **NIH NIH R35** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $382,090

## Abstract

PROJECT SUMMARY
Circadian rhythms drastically alter animal behavior through diverse actions on cellular targets throughout the
body. Disruptions of sleep-activity cycles account for a wide range of diseases affecting behavior, neurology,
metabolism, and muscle physiology. This proposal presents a set of studies designed to understand the
mechanisms and interactions of circadian effects on cells and systems spanning the body. Circadian rhythms
manifest downstream of pacemakers via signaling molecules that act directly on targets to regulate physiology.
Understanding how distinct targets are modified to achieve a constellation of physiological and behavioral
rhythms is a major goal in chronobiological research. We study how neurons, muscles, and biomechanics
interact in larval zebrafish, a tractable diurnal vertebrate, and our preliminary experiments suggest these animals
experience a breadth of circadian changes far more diverse than previously known. Although the zebrafish is an
imperfect model of sleep behavior, its clear circadian rhythms combined with its tractability for physiological,
behavioral, and genetic approaches make it an ideal system for understanding how circadian rhythms organize
and interact across cells and organs. We propose to define how diverse circadian effects on nervous system
output and muscle physiology amount to complex behavioral output, by tracking and modeling zebrafish behavior
and arousal across the diel cycle. We will manipulate light exposure to disentangle circadian and photic effects
on target systems, and we will use computational models to understand how circadian effects interact to shape
behavioral output. Furthermore, we will evaluate the breadth of circadian regulation of physiology across cellular
targets by performing in vivo electrophysiology and functional imaging. Combining this approach with cellular-
resolution transcriptional profiling enables us to define how circadian effector molecules signal divergently across
targets. Finally, we will test for interactions across circadian targets by examining rhythms following focal lesions
throughout the nervous system. Together these experiments will provide detailed information and models
regarding the interaction of circadian effects across cells and systems.

## Key facts

- **NIH application ID:** 10499448
- **Project number:** 1R35GM146885-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** DAVID Edward EHRLICH
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $382,090
- **Award type:** 1
- **Project period:** 2022-07-15 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499448

## Citation

> US National Institutes of Health, RePORTER application 10499448, Circadian regulation of brain and body in larval zebrafish (1R35GM146885-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499448. Licensed CC0.

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