# Whole-Brain Functional Imaging and Analysis of Zebrafish Sleep

> **NIH NIH UF1** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2022 · $3,210,336

## Abstract

ABSTRACT
Sleep occupies a third of our lives and sleep-related ailments cost an estimated $100 billion per year, yet the
mechanisms governing its regulation remain poorly understood. Despite the substantial progress that has been
made in the discovery and understanding of specific sleep-promoting and wake-promoting neuronal and
molecular pathways, what is missing is an integrated understanding of how these mechanisms work together in
the brain to regulate sleep and wake as whole-brain behavioral states. Toward this goal, we propose a
conceptually simple yet powerful approach: record the activity of every neuron in the brain during normal sleep
and wake states, and in response to perturbations that induce these states, then apply mathematical analysis
and modeling to uncover fundamental principles that underlie sleep. The main goals of this exploratory project
are to develop and validate imaging, analysis, and modeling tools that will serve as a foundation for a subsequent
larger-scale application that will comprehensively identify and characterize sleep-regulating circuits, and
generate models to explain the neuronal circuit principles that underlie sleep. We will use the small and
transparent larval zebrafish, a vertebrate model with well-characterized sleep behavior whose regulation is
conserved with that of mammals. Using this model and our custom-developed two-photon selective plane
illumination microscopy (2P-SPIM) platform, we will perform whole-brain recordings of neuronal activity with
cellular-resolution during both natural and induced sleep and wake states. We will then apply mathematical tools
to extract insights from these whole-brain recordings to identify the neural substrates that underlie sleep. Our
analysis will allow us to both test existing models of sleep regulation and to propose new models based on our
data. This project will be the first to achieve comprehensive observation and analysis of vertebrate sleep at such
scale and resolution. The unique insights gained from these studies will pave the way toward a more complete
understanding of the neuronal mechanisms that underlie sleep, whose dysfunction imposes a significant burden
on society.

## Key facts

- **NIH application ID:** 10430595
- **Project number:** 1UF1NS126562-01
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** GEOFFREY J GOODHILL
- **Activity code:** UF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $3,210,336
- **Award type:** 1
- **Project period:** 2022-05-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10430595

## Citation

> US National Institutes of Health, RePORTER application 10430595, Whole-Brain Functional Imaging and Analysis of Zebrafish Sleep (1UF1NS126562-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10430595. Licensed CC0.

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