# Roles of the Synapse in Hair-Cell Pathology

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $505,768

## Abstract

Project Summary
Noise exposure damages synaptic connections between cochlear inner hair cells and innervating auditory
nerves. Data from mammalian models and humans indicate that loss of some inner hair cell synapses can be
permanent, leading to the slow degeneration of detached auditory nerves. Yet recent research also supports
that the mammalian cochlea possesses the intrinsic capacity for hair cell synaptic repair following noise
damage. Defining the cellular mechanisms of synapse repair following traumatic noise is a critical step toward
identifying therapeutic targets to promote repair of hair cell synaptic contacts and prevent loss of auditory
nerves.
The overall goal of this proposal is to understand the molecular basis of morphological and functional hair cell
organ repair and recovery following noise-induced damage. Current gaps in our understanding of how hair cell
synapses repair following traumatic noise are in large part due to our inability to define the cellular processes
that promote synaptic repair in mammalian model systems. This project will circumvent these issues by
investigating mechecaniclly induced hair-cell synapse loss and subsequent repair in the zebrafish lateral line—
a mechanosensory organ which is made up of clusters of innervated hair cells. Zebrafish lateral-line hair cells
are comparable to mammalian hair cells at the molecular and cellular level, including a shared mechanism of
hair cell synapse loss and de-innervation following traumatic overstimulation. Yet lateral line hair cells rapidly
and unambiguously repair lost synaptic connections within hours following stimulus-induced damage. Aim 1 of
our proposal will test the hypothesis that hair cell activity governs synaptic repair, while Aim 2 will define the
contribution of inflammation to synaptic recovery and reinnervation. The results of each of our Aims will provide
information on how hair cell synaptic connections are restored following traumatic overstimulation and will help
identify strategies to promote endogenous repair in noise exposed cochlea, thereby preventing subsequent
auditory nerve degeneration and hearing loss.

## Key facts

- **NIH application ID:** 10931658
- **Project number:** 5R01DC016066-07
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Lavinia Sheets
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $505,768
- **Award type:** 5
- **Project period:** 2017-07-17 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931658

## Citation

> US National Institutes of Health, RePORTER application 10931658, Roles of the Synapse in Hair-Cell Pathology (5R01DC016066-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10931658. Licensed CC0.

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