# Molecular genetics of sensory modulation of motor programs

> **NIH NIH R35** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $586,885

## Abstract

PROJECT SUMMARY
Neuromodulators such as serotonin and neuropeptides can exert widespread and lasting effects on neural
circuits and behavior. This mode of signaling is critical for brain function. Dysfunctional neuromodulator signaling
causes a host neurological and psychiatric disorders, and neuromodulator signaling pathways are targets of
clinically important therapeutics and drugs of abuse. The goal of this project is to advance understanding of
molecular mechanisms that regulate the development and function of neuromodulatory systems that control
behavior. For this, we study the roundworm C. elegans, whose small and accessible nervous system is endowed
with most of the neuromodulators found in the human brain. Many behaviors of C. elegans require specific
neuromodulators and are amenable to genetic analysis, which permits unbiased discovery of factors required
for neuromodulator signaling or the development of neuromodulatory systems. We have found a circuit that
combines two types of neuromodulation to control a simple and stereotyped C. elegans behavior. Chemosensory
BAG neurons release neuropeptides that potently inhibit a pair of serotonergic neurons in the reproductive
neuromusculature of the C. elegans hermaphrodite - the HSNs. Through genetic studies of behaviors generated
by this circuit we have discovered genes required for the development and function of peptidergic BAGs and
factors required for neuropeptides to modulate HSN function and reproductive behavior. In addition to serving
as a model for neuromodulation, this circuit allows us to investigate the neurobiology of animal-microbe
interactions. BAG neurons detect the carbon dioxide generated by microbial respiration, and they function in a
circuit that evaluates the quality of environmental microbes and that allows C. elegans to discriminate between
nutritive microbes and pathogens. We have linked our interest in host-microbe interactions to our interest in
neuromodulation through a study of microbial metabolites that function as agonists of serotonin signaling to affect
animal behavior. To date our studies have revealed functions in the development and function of
neuromodulatory systems for a Toll-like receptor and its associated signaling pathway, insulin signaling,
evolutionarily conserved transcription factors, and regulators of neuronal excitability. Biochemical and genetic
screens based on these discoveries continue to yield new factors, and we expect that this circuit will continue to
serve as a powerful platform for understanding molecular mechanisms of neuromodulation.

## Key facts

- **NIH application ID:** 10414440
- **Project number:** 2R35GM122573-06
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Niels Ringstad
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $586,885
- **Award type:** 2
- **Project period:** 2017-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414440

## Citation

> US National Institutes of Health, RePORTER application 10414440, Molecular genetics of sensory modulation of motor programs (2R35GM122573-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10414440. Licensed CC0.

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