# Behavioral and physiological consequences of auditory nerve loss

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2024 · $640,934

## Abstract

Loss of hair-cell innervation by auditory-nerve fibers is a prevalent cochlear pathology in humans associated
with aging and sound overexposure, that does not impact audiometric thresholds in quiet. Called cochlear
synaptopathy, this inner-ear problem is widely expected to cause “hidden” hearing difficulties such as impaired
speech perception in noise. However, evidence that synaptopathy causes hidden hearing loss remains
controversial despite over a decade of intensifying research on the topic. Animal studies are well positioned to
advance this field because the approach allows direct induction of synaptopathy and targeted neural
recordings to identify underlying mechanisms. However, only a few studies have leveraged this approach. The
proposed study will clarify specific aspects of perception impacted by synaptopathy and underlying
mechanisms using animal behavioral experiments, auditory-nerve fiber recordings, and midbrain-neural
recordings in actively behaving animals. Experiments are conducted in budgerigars (parakeet) based on
adaptability of this species to operant-conditioning experiments and behavioral sensitivity similar to humans on
many simple and complex hearing tasks. Furthermore, accumulating evidence highlights conserved auditory
processing mechanisms between birds and mammals at peripheral and central levels. We test the novel
hypothesis that synaptopathy impairs perception of brief acoustic cues due to amplification of neural onset
responses, a nominal “gain of function” that we predict will degrade neural resolution of short signals due to
response saturation. This hypothesis is a significant departure from conventional theories based on low
spontaneous-rate fiber loss, which was not confirmed in a recent mouse study, and has direct relevance to
speech communication for which auditory analysis of short time periods is often critical. Furthermore, the
hypothesis is supported by recent auditory-nerve studies, and new preliminary data in budgerigars showing
that synaptopathy selectively degrades detection of tone bursts presented at the onset of a noise masker.
Synaptopathy is induced with kainic acid and validated histologically using established methodology. Additional
Aim-1 studies extend behavioral experiments into the critical realm of speech using synthesized consonants.
Aim-2 experiments use single-fiber auditory-nerve recordings to establish a firm baseline knowledge of how
synaptopathy impacts peripheral encoding and temporal dynamics. Aim 3 uses neural recordings from a key
midbrain processing center to determine the changes in central processing with synaptopathy; recordings from
actively behaving animals are analyzed with neural decision-variable correlations for maximum insight into
neural bases of normal and impaired perception. The detailed knowledge of specific perceptual deficits and
underlying changes in peripheral/central encoding provided by this work will help guide the development of
new public-health strateg...

## Key facts

- **NIH application ID:** 10877433
- **Project number:** 2R01DC017519-06
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Kenneth Stuart Henry
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $640,934
- **Award type:** 2
- **Project period:** 2019-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10877433

## Citation

> US National Institutes of Health, RePORTER application 10877433, Behavioral and physiological consequences of auditory nerve loss (2R01DC017519-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10877433. Licensed CC0.

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