# Synaptopathy and Suprathreshold Processing in Human Temporal Bone Cases with Normal or Elevated Thresholds

> **NIH NIH P50** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2021 · $393,487

## Abstract

Project 2 Summary - Abstract
 In acquired sensorineural hearing loss, the dogma has been that hair cells, as primary
targets, are the first to degenerate, and that cochlear nerve fibers die only after the hair cells
disappear. Recent animal work in the Kujawa and Liberman laboratories has shown, in both
noise-induced and age-related hearing loss, that the most vulnerable elements are actually the
synaptic connections between hair cells and cochlear neurons, and that this cochlear
synaptopathy can be widespread (> 50%) even in ears with no threshold elevation and no hair
cell degeneration. Synaptic loss silences the affected neurons, absent a cochlear implant,
however the slow death of the cell bodies and central projections offers a long therapeutic
window in which neurotrophin-related therapies could potentially reverse the damage. We
hypothesize that partial de-afferentation of surviving inner hair cells is widespread in acquired
sensorineural hearing loss and is a major cause of difficulties understanding speech in a noisy
environment, regardless of the degree of hair cell damage, as measured by the audiogram.
 A recent pilot study from the Liberman lab showed that the same immunostaining
techniques we developed to quantify cochlear synaptopathy in mouse, rat, guinea pig, rhesus
and other mammals can be applied to human post-mortem material. An analysis of a small
number of ears without explicit otologic disease revealed significant cochlear synaptopathy in
aged ears, despite no significant loss of hair cells. Here we propose to build on these
preliminary results to quantify, as broadly as possible, the prevalence of cochlear de-
afferentation in a wide range of hearing loss etiologies, using newly acquired human temporal
bones as well as archival sections from the Mass. Eye and Ear collection. Specifically we will,
quantify cochlear afferent and efferent innervation in age-graded “normal-hearing” subjects (Aim
1) and characterize cochlear synaptopathy in subjects with sensorineural hearing loss (Aim 2),
with etiologies including noise damage, aminoglycoside antibiotics, and cisplatin-based
chemotherapy. Completion of these foundational studies will reveal how widespread the
problem of primary neural degeneration is across the spectrum of sensorineural hearing loss in
human ears.

## Key facts

- **NIH application ID:** 10222644
- **Project number:** 5P50DC015857-05
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** M. Charles Liberman
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $393,487
- **Award type:** 5
- **Project period:** 2017-08-02 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10222644

## Citation

> US National Institutes of Health, RePORTER application 10222644, Synaptopathy and Suprathreshold Processing in Human Temporal Bone Cases with Normal or Elevated Thresholds (5P50DC015857-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10222644. Licensed CC0.

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