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.

Public Health Relevance

About 15% of Americans have hearing loss due to noise exposure. Here, we propose to use in vivo imaging of the mouse cochlea to determine how auditory nerves are damaged by loud sounds. The findings of this research may ultimately support a clinical trial in human subjects that attempts to treat hearing loss during the few hours after blast or noise trauma.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC017741-02
Application #
10053337
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
2020-01-01
Project End
2024-12-31
Budget Start
2021-01-01
Budget End
2021-12-31
Support Year
2
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Southern California
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089