# Cellular and Circuit Mechanisms of Neuropeptide Signaling

> **NIH NIH R35** · BUCK INSTITUTE FOR RESEARCH ON AGING · 2021 · $388,000

## Abstract

Parent Project Summary
The functions of the brain emerge from communication between neurons. The language of neuronal
communication is mediated by chemicals that are released from one neuron and sensed by another.
These chemical signals consistent of both classical “fast acting” neurotransmitters such as glutamate
and GABA that signal across synapses in milliseconds, as well as more than 100 diverse
neuromodulators that act on longer timescales. Neuromodulators are the major targets of most
neuropsychiatric drugs as well as drugs of abuse, and their dysregulation is implicated in medical
conditions ranging from obesity to psychiatric disorders. Yet we still lack a clear understanding, at both
the cellular and neural circuit level, of how these neuromodulators and their fast acting counterparts
cooperate to generate the diverse behavioral outputs of the brain. Neuropeptides are the largest and
most diverse class of neuromodulators that neurons use to communicate with each other and regulate
behavior. Yet we know little about the general rules that govern and constrain neuromodulatory
signaling in any organism. Here I propose to use the compact nervous system of C. elegans as a
unique paradigm to link neuropeptide signaling and neural circuits in a whole animal model. Despite its
anatomical simplicity, C. elegans makes rich use of neuropeptide signaling to regulate its behavior and
physiology and in shares a similar number of neuropeptide genes with mammals and a conserved set
of enzymatic pathways that regulate neuropeptide synthesis, processing, transport, and exocytosis. Our
goal is to discover, for the first time, how the biochemical network of neuromodulators relates to the
fixed anatomy of the brain in a whole animal model. Understanding this relationship is key to develop
tools to monitor brain activity, and ultimately to discover treatments for cognitive and behavioral
dysfunction. We will continue to pursue the parent grant project goals during the supplement period.

## Key facts

- **NIH application ID:** 10404451
- **Project number:** 3R35GM119828-05S1
- **Recipient organization:** BUCK INSTITUTE FOR RESEARCH ON AGING
- **Principal Investigator:** Jennifer L Garrison
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $388,000
- **Award type:** 3
- **Project period:** 2016-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10404451

## Citation

> US National Institutes of Health, RePORTER application 10404451, Cellular and Circuit Mechanisms of Neuropeptide Signaling (3R35GM119828-05S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10404451. Licensed CC0.

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