# Noise-Induced Synaptic Loss and Vestibular Dysfunction

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $204,355

## Abstract

Abstract
Vestibular dysfunction is a significant public health problem. Agrawal et al. (2009) reported that 35% of adults
older than 40 had evidence of postural instability. Balance dysfunction is linked to an increased likelihood of
falling and in the U.S. falls are responsible for more than 50% of accidental deaths. Although the causes of
vestibular dysfunction are multiple, recent studies suggest a linkage between noise-induced hearing loss and
vestibular dysfunction (Akin et al. 2012; Golz et al. 2001; Guest et al. 2011; Zuniga et al 2012). The suggestion
that noise exposure is also a risk factor for vestibular dysfunction is controversial as there is only limited
experimental support for causal relationships between noise exposure and peripheral vestibular pathology and
behavioral symptoms (e.g., poor balance). In our recently published study (Stewart et al. 2018), we exposed
rats to 6 hours of 120dB SPL low frequency noise (3-octave band centered at 1500Hz) and found that neural
activity in the vestibular nerve was reduced, as assessed by the vestibular short latency evoked potential
(VsEP). Noise exposed animals also exhibited reduced numbers of immunostained afferents with calyx
endings, especially calyx-only afferents that terminate on hair cells located in the striolar region of the sacculus
(Stewart et al. 2018). More recent experiments show that noise, depending on its intensity, can cause either
temporary or permanent threshold shifts of VsEP responses to jerk stimuli. Permanent noise induced VsEP
threshold shifts could reflect loss of calyces and/or concomitant loss of ribbon synapses within calyces. This
loss might be permanent or there could be recovery associated with reconnection of calyces or recovery of
synapses. We hypothesize that noise disrupts peripheral vestibular synapses and/or synaptic transmission,
transiently or permanently and causes functional vestibular loss.
Determining the basis for synaptic/signal transmission failure in the vestibular periphery and the parameters
that characterize damaging noise is a critical first step toward development of future preventative measures.
Specific Aim 1 will determine the parameters of noise that causes temporary versus permanent changes to
the VsEP and to peripheral vestibular nerve terminals and their synapses in the saccular and utricular
maculae. Specific Aim 2 will extend the analysis of Aim 1 to examine the semicircular canal cristae and
compare noise-induced changes in the cristae with those observed in the otolith organs. Specific Aim 3 will
correlate changes in VsEP responses and noise induced synaptic pathology with behavioral assays: a beam
crossing task, an otolith dependent behavior (macular ocular reflex, MOR), and a semicircular canal dependent
behavior (vestibuloocular reflex, VOR).

## Key facts

- **NIH application ID:** 10475946
- **Project number:** 3R01DC018003-02S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** WILLIAM M KING
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $204,355
- **Award type:** 3
- **Project period:** 2021-09-10 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475946

## Citation

> US National Institutes of Health, RePORTER application 10475946, Noise-Induced Synaptic Loss and Vestibular Dysfunction (3R01DC018003-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10475946. Licensed CC0.

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