# Auditory nerve synaptopathy and the central mechanisms underlying noise-induced hearing loss

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2024 · $479,425

## Abstract

PROJECT SUMMARY/ABSTRACT
 Noise-induced hearing loss (NIHL) is one of the most prevalent hearing conditions that affects people of
all ages. As a major risk factor, noise insult early in life accelerates auditory dysfunction and exacerbates hearing
loss with age. Understanding the mechanisms of NIHL at early stages is crucial for the development of clinical
interventions to prevent or ameliorate permanent damage of the auditory system. Pathophysiology of NIHL has
been mostly reported in the cochlea, including detrimental changes in the sensory hair cells, the spiral ganglion
neurons (SGN), and the cochlear synapses connecting the two. One significant finding was that cochlea
synapses of the low spontaneous rate SGNs are vulnerable and can be preferentially damaged by noise,
preceding the occurrence of permanent overt hearing loss. It remains unclear how such noise-induced peripheral
changes link to structural and functional alterations in the central auditory system in contributing to compromised
hearing perception. As the only target for all SGNs and the starting site of central auditory processing, the
cochlear nucleus (CN) is expected to alter in morphology and physiology after noise insult in conjunction with
selective SGN changes and impact the signal processing of the entire central auditory system. The long-term
goal of this project is to elucidate the central mechanisms of NIHL in the CN by identifying noise-induced
synaptopathy at the auditory nerve (AN) central synapses from different subtypes of SGNs, and clarifying the
impact on the structure and function of the CN circuits. We hypothesize that AN synapses from low spontaneous
rate SGNs are subject to more profound synaptopathy upon noise insult, which lead to more dramatic
morphological and physiological changes in linked CN neurons with altered neural processing that contribute to
NIHL. We further postulate that AN synapses from high spontaneous rate SGNs and linked CN neurons are
unchanged during hidden hearing loss caused by moderate noise exposure, but damaged during overt hearing
loss after traumatic noise exposure. Combining electrophysiology with immunohistochemistry in genetically
modified mice, this project investigates the structure and function of identified AN synapses and neurons in CN
circuits after moderate or traumatic noise exposure. In Aim1, we will identify noise-induced AN central
synaptopathy both morphologically and physiologically at the giant endbulb of Held synapses from different
subtypes of type I SGNs. In Aim 2, we will characterize noise-induced changes in cellular morphology and
physiological properties of CN principal bushy neurons, and identify the altered CN output during NIHL. In Aim
3, we will elucidate the mechanisms of NIHL in CN inhibitory neural network by characterizing the noise-induced
synaptopathy at AN bouton synapses onto D-stellate neurons and identifying the weakened inhibition onto CN
bushy neurons. The outcome of this project will fill...

## Key facts

- **NIH application ID:** 10864958
- **Project number:** 5R01DC020582-03
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Ruili Xie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $479,425
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10864958

## Citation

> US National Institutes of Health, RePORTER application 10864958, Auditory nerve synaptopathy and the central mechanisms underlying noise-induced hearing loss (5R01DC020582-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10864958. Licensed CC0.

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