# The function of gap junctions and chemical synapses in a simple neural circuit

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2020 · $402,305

## Abstract

C. elegans locomotion neural circuit is an excellent model for decoding the circuit and gene bases of behaviors.
Previous studies have produced a detailed wiring diagram of this circuit, and proposed that two pairs of premotor
interneurons, AVA and AVB, play key roles in locomotion by activating A-type and B-type cholinergic motor
neurons (A-MNs and B-MNs), respectively. However, how the various neurons interact at the synaptic level is
largely unknown. Our recent success in voltage-clamping motor neurons and recording gap junction currents
between neurons in worms makes it possible to look into properties of the circuit that are otherwise inaccessible.
Our preliminary studies revealed several unexpected and novel properties of the locomotion circuit, including
retrograde gap junction currents between the premotor interneurons and motor neurons, a putative
degenerin/epithelial sodium channel (DEG/ENaC) serving as a stretch receptor in B-MNs, retrograde regulation
of the backward circuit by GABAergic MNs (D-MNs), and electrical coupling between the left and right AVA
interneurons. This proposal is to use a combination of electrophysiological, genetic, molecular, and behavioral
approaches to test a new model with three specific aims. Aim 1 is to test the hypotheses that B-MNs activate
AVB premotor interneurons through gap junctions, and that B-MN activity depends on a stretch receptor. We will
determine molecular mechanisms of the gap junction rectification and the effects of deficient electrical coupling
on AVB activity and locomotion behavior. We will identify the putative DEG/ENaC in B-MNs and determine its
roles in B-MN activity and locomotion. Aim 2 is to investigate the mechanism of the rectifying coupling between
AVA and A-MNs, and the physiological role of electrical coupling between the left and right AVA interneurons.
We will determine whether the rectification is conferred by the N-terminal of UNC-7 innexin in AVA and whether
disrupting the coupling between AVA interneurons alters locomotion behavior. Aim 3 is to test the hypotheses
that D-MNs inhibit A-MNs retrogradely via AVA, and that AVB facilitates forward locomotion by inhibiting AVA.
We will assess the effect of disrupting the novel D-MN inhibitory circuit on locomotion. We will identify the
postsynaptic receptors mediating AVB inhibition on AVA, and analyze the effect that disrupting this receptor has
on locomotion. This project may reshape our understanding of the C. elegans locomotion neural circuit, and
help us approach the long-term goal of elucidating the circuit and gene bases of behaviors.

## Key facts

- **NIH application ID:** 9994399
- **Project number:** 5R01NS109388-03
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** ZHAO-WEN WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,305
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994399

## Citation

> US National Institutes of Health, RePORTER application 9994399, The function of gap junctions and chemical synapses in a simple neural circuit (5R01NS109388-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9994399. Licensed CC0.

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