# Plasticity of auditory electrical synapses

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $565,874

## Abstract

Abstract
Gap junction (GJ)-mediated electrical synapses were recently reported to underlie important network
properties in the dorsal cochlear nucleus and anatomical evidence suggests they are widespread along the
auditory pathway. However, the properties of auditory electrical synapses remain poorly understood. As their
chemical counterparts, electrical synapses are ‘plastic’, that is, they modify their strength with activity. Changes
in the strength of electrical synapses dynamically reconfigure neuronal circuits in various neural structures.
Thus, the presence and plastic properties of electrical synapses could fundamentally change the way we
understand the organization of auditory circuits and, ultimately, the processing of auditory information. This
proposal aims to contribute to our understanding of electrical transmission in the auditory system by
investigating the molecular mechanisms causing plastic changes in GJ communication at mixed, electrical and
chemical, contacts that couple primary auditory afferents to the Mauthner (M-) cells in fish. Our work in goldfish
shows that electrical (and chemical) transmission at these mixed synapses undergo activity-dependent
potentiation. Because these dynamic properties were later found to occur at mammalian electrical synapses.
M-cell mixed synapses are considered a valuable model to study plasticity of vertebrate electrical transmission.
In contrast to chemical synapses, little is known about the molecular mechanisms that underlie changes in the
strength of electrical synapses. It is currently thought that plastic changes in GJ conductance are due to direct
modification of the properties of already existing channels. However, our progress suggests that regulated
insertion and removal of GJ channels may also contribute to plasticity. We propose to investigate the
contribution of regulated trafficking of GJ channels to plastic changes of electrical transmission and its
molecular underpinnings. To directly examine this possibility, we will take these unique model mixed synapses
to a new level of analysis by investigating their properties in larval zebrafish. The amenability of zebrafish
larvae to image the movement of fluorescently-tagged GJ channels in-vivo should allow monitoring of active
synapses undergoing plasticity. This approach will provide an unprecedented window for the analysis of
electrical transmission at which detailed molecular mechanisms will be investigated by combining in-vivo
imaging, electrophysiology and time-resolved ultrastructural analysis with powerful genetic manipulations. Aim
1 is to investigate the conditions under which electrical synapses in larval zebrafish undergo potentiation. By
combining electrophysiology and pharmacology with electrical and optogenetic stimulation, this aim will identify
the conditions under which larval mixed synapses undergo potentiation of electrical (and chemical)
transmission. Aim 2 is to test whether insertion and removal of GJ channels ar...

## Key facts

- **NIH application ID:** 9889922
- **Project number:** 5R01DC011099-11
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Alberto E Pereda
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $565,874
- **Award type:** 5
- **Project period:** 2010-07-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889922

## Citation

> US National Institutes of Health, RePORTER application 9889922, Plasticity of auditory electrical synapses (5R01DC011099-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9889922. Licensed CC0.

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