# Mechanisms of cochlear synaptopathy after noise or blast trauma

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $673,715

## Abstract

Project Summary/Abstract
About 15% of Americans have hearing loss due to noise exposure. The classical explanation is trauma to the
cochlear hair cells. An additional mechanism of noise-induced hearing loss is cochlear synaptopathy. There
are no effective treatments used clinically to prevent hearing loss via either mechanism after traumatic noise
exposure. Recently, we identified that endolymphatic hydrops occurs after blast or noise trauma, and that
endolymphatic hydrops correlated with cochlear synaptopathy. Our central hypothesis is that endolymphatic
hydrops is a surrogate marker for swelling of auditory nerve dendrites that occurs in response to glutamate
excitotoxicity. We will test this hypothesis with three aims. First, we will determine whether swelling of auditory
nerve dendrites correlates with endolymphatic hydrops. We will measure the volume of scala media in vivo
using volumetric optical coherence tomography and vibrometry (VOCTV). We will simultaneously image
auditory nerve fiber terminals in vivo with two-photon microscopy and measure their diameter. Second, we will
determine whether acute hair cell dysfunction is necessary to produce the physiological consequences of
cochlear synaptopathy. We will measure basilar membrane vibratory tuning curves using VOCTV to assess
cochlear physiology. We will also measure the wave 1 auditory brainstem response (ABR) peak-to-peak
amplitude to assess auditory nerve physiology. Third, we will determine whether the inciting mechanism of
cochlear synaptopathy is glutamate, endolymphatic hydrops, or dendritic swelling. We will measure scala
media volume, cochlear gain, and synaptic counts after noise or hypotonic challenge in mice with impaired
transduction or impaired glutamate release at the IHC-auditory nerve synapse. Therefore, we are proposing to
definitively prove or disprove our hypothesis. Furthermore, we will understand the physiological consequences
and mechanisms of endolymphatic hydrops and synaptopathy.

## Key facts

- **NIH application ID:** 10053337
- **Project number:** 5R01DC017741-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** John S Oghalai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $673,715
- **Award type:** 5
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10053337

## Citation

> US National Institutes of Health, RePORTER application 10053337, Mechanisms of cochlear synaptopathy after noise or blast trauma (5R01DC017741-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10053337. Licensed CC0.

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