# Activity-dependent regulation of auditory nerve synapses in the cochlear nucleus

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $335,141

## Abstract

Project Summary
Both loud noise and conductive hearing loss can have long-term detrimental effects on hearing. The possible
mechanisms have primarily been studied at high-order stages of the auditory pathway, but effects early in the
pathway are relatively unknown, despite the likelihood that changes there could have consequences for all
downstream processing. We found that sound-driven activity triggers a novel, slow adaptation mechanism
that alters the properties of auditory nerve synapses, which are at the very start of the central auditory
pathway. Within a week’s exposure to an augmented sound environment, auditory nerve synapses have
reduced depression and expanded structure, as well as enhanced spiking in the postsynaptic bushy cells,
which combine to enhance fidelity to synaptically-driven activity. By contrast, after one week of occluding the
ear canal, auditory nerve synapses have increased depression and reduced size, with reduced spiking and
fidelity in bushy cells. These changes are surprising, because it has long been thought that the early auditory
pathway was unaffected by sensory experience, except under extreme, pathological conditions. This raises the
possibility that this mechanism could be involved in disorders such as tinnitus and otitis media. Therefore, it is
important to understand how this mechanism is normally triggered and what mechanisms underlie it. Aim #1
will examine the susceptibility of auditory nerve synapses to abnormal sound levels, in terms of age and
duration of exposure. Aim #2 will use in vitro methods to uncover the mechanisms underlying the changes in
synaptic function. Aim #3 will examine the functional consequences for synaptic fidelity, both in vitro and in
vivo. Studying this mechanism will lead to new understanding of how synapses are normally regulated, as
well as new treatments for disorders caused by abnormal activity, including tinnitus and otitis media.

## Key facts

- **NIH application ID:** 10092149
- **Project number:** 5R01DC015508-05
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** MATTHEW A. XU-FRIEDMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $335,141
- **Award type:** 5
- **Project period:** 2017-03-01 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10092149

## Citation

> US National Institutes of Health, RePORTER application 10092149, Activity-dependent regulation of auditory nerve synapses in the cochlear nucleus (5R01DC015508-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10092149. Licensed CC0.

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