# Auditory nerve central synaptopathy during noise-induced hearing loss

> **NIH NIH R56** · OHIO STATE UNIVERSITY · 2021 · $157,500

## Abstract

PROJECT SUMMARY/ABSTRACT
 Sound information is transmitted from the peripheral cochlea to the central auditory system via two key
synapses, including the cochlear synapse and auditory nerve (AN) synapse, which are the peripheral and central
endings of the spiral ganglion neurons (SGNs), respectively. Selective cochlear synaptopathy among different
subtypes of SGNs has been recognized as a main mechanism of hearing loss, one of the most common forms
of which is noise-induced hearing loss (NIHL). Cochlear synapses from SGNs of the low spontaneous rate/high
threshold subtype are especially vulnerable and can be preferentially damaged by even moderate noise insult,
which are likely the primary cause of the perceptual deficit, especially during hidden hearing loss. At the SGN
central endings, however, the mechanisms of NIHL remain largely unclear. Little is known about how AN
synapses from different subtypes of SGNs change in morphology and physiology during NIHL, and how such
central synaptopathy contributes to the central processing deficits in target neurons in the cochlear nucleus (CN).
The long-term goal of this project is to elucidate the mechanisms of NIHL at different subtypes of AN synapses
and their target CN neurons. Our overall hypothesis is that AN synapses from different subtypes of SGNs have
unique synaptic properties, target distinct populations of CN neurons that are dedicated to processing different
aspects of sound information, and subject to different levels of synaptopathy during NIHL that lead to distinctive
central auditory processing deficits among associated CN neurons. Combining electrophysiology with
immunohistochemistry using transgenic mice, this project investigates selective synaptopathy at different
subtypes of AN synapses during NIHL, as well as the associated central processing deficits in their target CN
neurons. In Aim1, we will identify AN central synaptopathy both morphologically and physiologically at the giant
endbulb of Held synapses from three subtypes of type I SGNs after two different levels of noise damage. In Aim
2, we will elucidate the mechanisms of central processing deficits in CN bushy neurons following selective AN
synaptopathy during NIHL. In Aim 3, we will elucidate the mechanisms of NIHL in CN inhibitory neural network
by characterizing synaptopathy of AN bouton synapses onto D-stellate neurons and clarifying the changes of
their output inhibition onto CN bushy neurons during NIHL, especially hidden hearing loss. The outcome of the
project will fill our knowledge gap on AN central synaptopathy as well as the mechanisms of central processing
deficits in target CN neurons during NIHL.

## Key facts

- **NIH application ID:** 10412432
- **Project number:** 1R56DC019093-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Ruili Xie
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $157,500
- **Award type:** 1
- **Project period:** 2021-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412432

## Citation

> US National Institutes of Health, RePORTER application 10412432, Auditory nerve central synaptopathy during noise-induced hearing loss (1R56DC019093-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10412432. Licensed CC0.

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