# Synaptopathy, Neural Pathophysiology and Suprathreshold Processing in Gerbils with Normal or Elevated Thresholds

> **NIH NIH P50** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2020 · $507,601

## Abstract

Project 1 Summary – Abstract
 In common causes of human hearing loss like aging and noise exposure, permanent threshold losses are
associated with permanent cochlear injury, often hair cell damage or loss. Recently, work in animal models has
revealed what may be a more common consequence of these and other causes of acquired sensorineural
hearing loss. This work has shown that synapses between inner hair cells (IHCs) and cochlear neurons are
most vulnerable, with their loss interrupting sensory-to-neural communication long before loss of the hair cells
themselves, and long before sensitivity losses appear on the threshold audiogram. The silencing of affected
neurons that results is a likely contributor to a variety of auditory perceptual abnormalities, including speech-in-
noise difficulties, tinnitus and hyperacusis that can occur with or without threshold sensitivity loss.
 As these findings are translated to the study of human hearing loss, animal models will continue to provide
a powerful approach to test hypotheses, to characterize structural and functional consequences of carefully-
titrated manipulations and to evaluate the sensitivity of the assessments to the underlying histopathology.
Here, animal models of sensorineural hearing loss etiologies common in humans; exposure to noise, to
aminoglycoside antibiotics and to platinum-containing chemotherapeutics, will be created. The models will
address the mixed (sensory + neural) pathology that will likely be present in many of the humans and human
temporal bones evaluated in the other Projects. The human test battery will be applied (Aim 2) and its
diagnostic power assessed by directly measuring the underlying cochlear histopathology (Aim 1). Structure-
function correlations will be probed further using detailed electrophysiologic assays that might be streamlined
for future clinical use (Aim 3). Work will be performed in gerbil, a species with good low frequency hearing and
can be trained to perform auditory tasks. By correlating performance on these complex listening tasks with
electrophysiology in the same subjects and with explicit measurement of the underlying synaptopathy, the
contribution of cochlear neuropathy to the perceptual declines can be quantitatively evaluated and results can
be directly compared to those obtained in human subjects.
 An improved understanding of the extent to which synaptic mechanisms are damaged in common forms of
human sensorineural hearing loss will have broad implications for efforts to identify drugs or other treatments
with the potential to target these mechanisms for prevention or rescue. Practically, this knowledge will inform
clinical diagnostics, the monitoring of new treatments for efficacy or the monitoring of individuals at risk of
hearing compromise from drug and noise exposure. It also may help explain auditory performance differences
among individuals with the same audiometric configurations, even for those with normal thresholds.

## Key facts

- **NIH application ID:** 9987320
- **Project number:** 5P50DC015857-04
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Sharon G Kujawa
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $507,601
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987320

## Citation

> US National Institutes of Health, RePORTER application 9987320, Synaptopathy, Neural Pathophysiology and Suprathreshold Processing in Gerbils with Normal or Elevated Thresholds (5P50DC015857-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9987320. Licensed CC0.

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