# Gap Junction-Mediated Regulation of Nociceptive Sensory Signaling

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $336,706

## Abstract

Studying the logic of small neural circuits is an essential step toward understanding more
complex circuits and, ultimately, the computational and integrative properties of whole nervous systems.
With a compact nervous system (just 302 neurons) and a well-characterized behavioral repertoire, the
small roundworm C. elegans serves as an excellent animal model to study circuit-level modulation of
neuronal function. While chemical synapses allow neurons to communicate with each other through the
vesicular release of neurotransmitters into synaptic clefts between the cells, gap junctions allow for direct
cytoplasmic communication and electrical coupling between neurons. As such, gap junctions are often
referred to as electrical synapses. Importantly, the presence of gap junctions in the nervous system
allows for the establishment of even more complex circuits than can be generated by synaptic signaling
alone. We have identified a non-cell-autonomous role for guanylyl cyclases in the regulation of
nociceptive sensory behaviors, and have gathered evidence for circuit-level modulation of neuronal
activity by movement of the second messenger cGMP through gap junctions. As an important step
towards our long-term goal of understanding how cellular and intercellular mechanisms interact within
neural circuits to control animal behavior, the overall objective of this application is to determine the
mechanism by which select guanylyl cyclases modulate nociceptive behavioral responses in C. elegans.
Herein we propose to use a combination of genetic, behavioral and neuronal imaging approaches in C.
elegans to establish how cGMP generation and movement through gap junctions regulates nervous
system function. We will: (1) use in vivo imaging to characterize cGMP and Ca2+ dynamics in a sensory
neural circuit, (2) determine the mechanism by which specific guanylyl cyclases modulate ASH
nociceptor sensitivity non-cell-autonomously, and (3) define the network(s) of gap junction components
that coordinate to pass cGMP to modulate ASH nociceptor sensitivity. Together, these studies will
delineate a new means of neuronal communication and a new mechanism for the coordination and
optimization of animal behavior. This information is required to develop innovative pharmacological
approaches to modulate gap junction signaling for therapeutic goals.

## Key facts

- **NIH application ID:** 9827982
- **Project number:** 5R01DC015758-04
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Denise Marie Ferkey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $336,706
- **Award type:** 5
- **Project period:** 2016-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9827982

## Citation

> US National Institutes of Health, RePORTER application 9827982, Gap Junction-Mediated Regulation of Nociceptive Sensory Signaling (5R01DC015758-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9827982. Licensed CC0.

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