# Cochlear synaptopathy, neural pathophysiology and suprathreshold processing in animal models of sensorineural hearing loss

> **NIH NIH P50** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2022 · $578,395

## Abstract

Project 1 Summary - Abstract
 Animal studies of acquired sensorineural hearing loss (SNHL) have shown that loss of
synapses between auditory nerve fibers (ANFs) and inner hair cells (IHCs) often occurs before
permanent hair cell damage. This primary cochlear nerve degeneration (CND) has little effect
on thresholds, but decreases discriminability of sounds, especially in noisy environments, and
may trigger tinnitus and hyperacusis due to changes in excitation/inhibition in central auditory
circuits. In prior work, Project 1 showed that several suprathreshold electrophysiological metrics
can predict synaptic loss in animals when thresholds are normal, and Project 3 showed that
these metrics correlate with word-identification performance in challenging listening
environments among subjects with normal audiometric thresholds, consistent with a role for
CND in hearing impairment that hides behind the audiogram.
 Over the next 5 years, all Center Projects shift focus to the study of CND in cases where
thresholds are elevated. Consistent with the intent of the P50 mechanism, the primary role of
Project 1 animal work is in support of the human studies. To that end, we have developed a set
of animal models with complementary patterns of neural and hair cell damage. In Aim 1 we use
these models to: 1) clarify the cellular generators of the summating potential, the biomarker
best correlated with word scores in human subjects, 2) validate the utility of a novel
electrophysiologic metric, the envelope following response to rectangular-wave amplitude
modulation, in detecting CND in the presence of outer hair cell damage, and 3) determine
whether the different CND-eliciting lesions all selectively target cochlear neurons with high
thresholds and low spontaneous rates. For Aim 2, we have developed a novel
electrophysiological assay of central auditory hyperactivity (that will also be used in human
subjects) and a set of behavioral assays to detect changes in loudness perception and the
presence of phantom sounds. By applying these assays to animals with different lesion
patterns, we can test key hypotheses about the interactions between peripheral CND, central
gain control adjustments, and the disabling perceptual anomalies of tinnitus and hyperacusis.

## Key facts

- **NIH application ID:** 10422248
- **Project number:** 2P50DC015857-06
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Sharon G Kujawa
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $578,395
- **Award type:** 2
- **Project period:** 2017-08-02 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10422248

## Citation

> US National Institutes of Health, RePORTER application 10422248, Cochlear synaptopathy, neural pathophysiology and suprathreshold processing in animal models of sensorineural hearing loss (2P50DC015857-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10422248. Licensed CC0.

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