# Equipment Supplement:  Mechanisms that drive the variation of aversive behavior

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $249,754

## Abstract

PROJECT SUMMARY
How behavior is regulated is a fundamental unsolved problem. Approaching this problem requires tractable
behavioral readouts. It also requires model systems that are amenable to molecular genetic and systems level
dissection. The long-term goal of this project is to elucidate the molecular and cellular basis of aversive
behavior, an action that is propelled by un-wanting, “dislike”, or fear. Understanding how aversive behavior is
regulated at the basic molecular, cellular, systems, and population levels shall provide fundamental insights
into our understanding of brain function, and are therefore of high significance.
 Larval zebrafish provide a salient vertebrate system that enables the understanding of behavior from
molecules to systems. For example, they exhibit a light/dark preference behavior, with dark being perceived
aversive. Light/dark preference as a choice behavior is observed across the animal kingdom. The underlying
mechanisms are however not understood. In mammals, light/dark preference is considered an anxiety-like trait
and used to assess the anxiolytic properties of drugs. Intriguingly, treatment of larval zebrafish with the same
anti-anxiety medications also significantly relieves their dark aversion.
 We have demonstrated heritable variation of the dark aversion behavior in larval zebrafish. In this
application, we propose to exploit the unique strengths of larval zebrafish for high throughput
phenotyping/genotyping and brain-wide calcium imaging. We will team up with experts in population genetics
and computational science to understand the molecular and cellular basis of this behavioral variation. The
central objectives of this proposal are: 1) Determine, at the molecular genetic level, the driving forces for this
behavioral variation. 2) Uncover cellular and network level mechanisms that underlie this behavioral variation.
Successful completion of these aims will link genes to brain and to behavior.
Impact and Outcomes: Complex behaviors are observed in a spectrum across the population, with the
extreme ends of the spectrum often classified as disease states. The proposed work harvests a unique
resource of behavioral variation in a tractable vertebrate model organism, and is expected to uncover new and
potentially evolutionarily conserved insights into behavioral regulation. These findings should have a positive
impact on informing human studies of behavioral variation ranging from normal spectrum to disease states.
The proposed work also lay foundation for other researchers to use zebrafish for mapping naturally existing
quantitative traits.

## Key facts

- **NIH application ID:** 10135446
- **Project number:** 3R01GM132500-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Su Guo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,754
- **Award type:** 3
- **Project period:** 2019-09-16 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135446

## Citation

> US National Institutes of Health, RePORTER application 10135446, Equipment Supplement:  Mechanisms that drive the variation of aversive behavior (3R01GM132500-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10135446. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*