# Neuromodulator signaling and activity in the C. elegans egg-laying circuit

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $413,750

## Abstract

Project Summary
The long-term goal of this project is to delineate at an unprecedented level of precision how all the
neurotransmitter signaling events within a model neural circuit together produce its dynamic pattern of activity.
Neural circuits are a basic unit of brain function, and altered signaling within neural circuits can disrupt circuit
function to produce mood disorders and other human brain diseases. To date, our understanding of such
diseases remains vague because we understand only a few individual features within each of the many
different neural circuits that have been studied. Therefore, our approach is to analyze all the signaling events
within one simple neural circuit, anticipating that this will yield new insights into how neural circuits in general
work. This approach is inspired by past successes in other areas of biology in which deep analysis of a simple
model in a genetically tractable organism (e.g. the lac operon in E. coli or pattern formation in the Drosophila
embryo) led to conceptual breakthroughs that generalized to human biology. Thus, we are intensely studying
the simple egg-laying circuit of C. elegans, an experimental system in which we have developed a powerful
combination of genetic, optogenetic, chemogenetic, and Ca2+ imaging approaches that together can provide
unprecedented mechanistic insights into circuit function. Our analysis has already discovered two instances in
which a small-molecule neurotransmitter signals alongside co-released neuropeptides, and also that ongoing
circuit activity responds to homeostatic feedback from the postsynaptic cells. These features are likely
conserved in other neural circuits. In the next period of this project we aim to understand how the egg-laying
circuit turns itself on. This circuit alternates between ~20 minute inactive phases and ~2.5 minute periods of
rhythmic activity. Our recent work shows that the two HSN command neurons release a combination of
serotonin and neuropeptides encoded by the nlp-3 gene to activate the circuit. These neuromodulators signal
through a set of at least five receptors to alter the postsynaptic muscle response to acetylcholine released from
presynaptic motor neurons.
Aim 1. We will determine how the HSN neurons “decide” when to release serotonin and NLP-3 neuropeptides
 to activate the circuit.
Aim 2. We will determine how a diverse set of receptors for serotonin and NLP-3 neuropeptides alter activity of
 various specific cells of the circuit to make the circuit active.
Aim 3. We will identify the cells and signals that act with HSN-released serotonin and NLP-3 neuropeptides to
 help activate the circuit and ultimately trigger egg-laying muscle contraction.

## Key facts

- **NIH application ID:** 9939723
- **Project number:** 5R01NS086932-06
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Kevin Michael Collins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $413,750
- **Award type:** 5
- **Project period:** 2014-09-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939723

## Citation

> US National Institutes of Health, RePORTER application 9939723, Neuromodulator signaling and activity in the C. elegans egg-laying circuit (5R01NS086932-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9939723. Licensed CC0.

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