# Development and Validation of a Genetically Encoded Method to Trace and Manipulate Neuronal Circuits in Zebrafish

> **NIH NIH RF1** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2022 · $2,440,479

## Abstract

PROJECT SUMMARY
Identifying how neurons are connected to each other in the brain is an important and necessary step towards
understanding how brain activity gives rise to behavior, and how it is perturbed by disease. Unfortunately,
currently available methods have limitations that make it challenging to visualize these brain wiring diagrams. In
addition, there is an urgent need for a method that will make it possible not only to unveil brain connectivity, but
also to genetically modify the functional properties of neurons connected in a circuit. We recently developed a
genetic system named TRACT and showed using Drosophila that it possesses both of these features. However,
many complex brain functions cannot be examined in Drosophila, and understanding them will require the use
of vertebrate animals. In recent years the zebrafish has emerged as a useful vertebrate animal model to study
complex brain processes due to its relatively simple yet conserved vertebrate brain, optical transparency during
embryonic and larval stages of development, amenability to large-scale behavioral assays, the emergence of
complex behaviors after only 5 days of development, and a growing suite of genetic tools that allow observation
and manipulation of neuronal circuits in behaving animals. However, the usefulness of zebrafish for neuroscience
research is constrained by a lack of methods to identify and perturb synaptically connected neurons. In
preliminary studies, we developed a TRACT system that can be used to identify anterograde monosynaptic
connections between neurons in the zebrafish brain. Here we propose to further develop TRACT as a tool for
transneuronal tracing in zebrafish by developing additional anatomical tracing modalities, and by establishing
the use of TRACT to genetically manipulate and functionally characterize synaptically connected neurons. These
capabilities will increase the usefulness of zebrafish as a model system to study vertebrate neuronal circuit
function, both to reveal general principles of neuronal circuits that underlie specific behaviors, and to model
complex brain disorders such as autism, Alzheimer’s disease and schizophrenia.

## Key facts

- **NIH application ID:** 10505822
- **Project number:** 1RF1MH130420-01
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** CARLOS LOIS
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,440,479
- **Award type:** 1
- **Project period:** 2022-08-19 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10505822

## Citation

> US National Institutes of Health, RePORTER application 10505822, Development and Validation of a Genetically Encoded Method to Trace and Manipulate Neuronal Circuits in Zebrafish (1RF1MH130420-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10505822. Licensed CC0.

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