# Dissecting neural mechanisms integrating multiple inputs in C.elegans

> **NIH NIH R01** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2021 · $481,000

## Abstract

Summary
Atypical sensory-based behaviors are a common feature of a number of human conditions, including autism
spectrum disorder, schizophrenia, fragile X, etc. Despite this, little is known about how the genes associated with
these conditions affect sensory behavior. A complete understanding of this process requires a thorough
characterization of the underlying neural circuitry, along with the ability to measure and perturb the activity of
these circuits. The nematode, Caenorhabditis elegans, provides a unique opportunity to analyze genes, cells,
and circuits regulating complex behaviors, as its nervous system consists of just 302 neurons interconnected via
identified synapses that utilize highly conserved synaptic machineries. The Chalasani lab has shown that C.
elegans homologs of the human autism-associated genes (neurexin (NRX) and neuroligin (NLG)) affect
sensitivity to specific sensory stimuli, and that mutations in these genes result in hyposensitivity to a repellent
copper stimulus. They propose to identify the specific C. elegans synapses where these two synaptic proteins
function to modify sensory behaviors. Additionally, they plan to identify the developmental time window in which
these genes are required to generate a typically behaving young adult (Aim 1). Moreover, they have shown that
sensory defects associated with neuroligin mutants (nlg-1) are rescued by mutations in the gene npr-1, a gene
that when mutated alone results in a “social” aggregation behavior. They propose to identify the neural
mechanisms that underlie this interaction and reveal components of the NPR-1 signaling pathway that act to
suppress nlg-1 behavioral defects (Aim 2). Finally, they have identified Nipecotic acid and CGP-13501 as
candidate small molecules that suppress nlg-1 behavioral deficits. They plan to map the cellular and molecular
targets of these drugs in C. elegans, analyzing the genetic pathways modifying NRX-1/NLG-1 signaling in this
model (Aim 3). These studies will reveal mechanisms by which NRX-NLG signaling modifies sensory behavior
at the level of genes, synapses, circuits, and whole animals, providing a solid foundation for further analyses in
vertebrate models. As both NLG and NRX have been implicated in autism spectrum disorder, results may shed
light on molecular and circuit mechanisms underlying human disorders that have been linked to abnormalities in
sensory processing.

## Key facts

- **NIH application ID:** 10197766
- **Project number:** 5R01MH096881-09
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Sreekanth H. Chalasani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $481,000
- **Award type:** 5
- **Project period:** 2012-12-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197766

## Citation

> US National Institutes of Health, RePORTER application 10197766, Dissecting neural mechanisms integrating multiple inputs in C.elegans (5R01MH096881-09). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10197766. Licensed CC0.

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