# Peripheral vestibular hypofunction and neurosensory coding

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $642,108

## Abstract

Project Summary
 The proposed research addresses critical issues of high translational importance concerning the
mechanisms and outcomes of partial dysfunction of the vestibular sensory epithelia, referred to as peripheral
vestibular hypofunction. The research plan utilizes chemotoxin- induced hypofunction, the foundation for which
was identified through recent work from the PI’s laboratory in an animal model enabling precise
intraperilymphatic dosing resulting in the production of highly reproducible lesions. This provides the basis for
producing lesions of graded magnitudes within the sensory neuroepithelia, documented through
histopathologic analyses. The physiologic outcome of these lesions will be evaluated through recordings of
single afferent neuron electrophysiology and the vestibulo-ocular reflex, providing the bases for establishing
histologic and physiologic correlates to a direct behavioral test of vestibular function. Previous work has
demonstrated that the afferent neuron calyx is highly labile to pathologic compromise, and owing to its
important contribution to shaping neural dynamics in untreated epithelia it is a focus for assessing pathologic
damage. The present research plan will enable the direct correlate of afferent discharge dynamics to critical
cellular components of the calyx, including its morphology and expression of KCNQ4 and sodium-potassium
ATPase. In addition, we will examine the distribution of synaptic ribbons within hair cells of lesioned epithelia,
testing whether a systematic synaptopathy also contributes to the compromised vestibular function. In
summary, the present investigation provides critical insight into the histopathologic substrates of vestibular
hypofunction and the alterations in sensory coding that underlies the functional compromise. At the same time,
however, this investigation will reveal important cellular and physiologic metrics that are required for normal
vestibular function, addressing longstanding question in vestibular neurobiology.

## Key facts

- **NIH application ID:** 10186081
- **Project number:** 1R01DC019459-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** LARRY F HOFFMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $642,108
- **Award type:** 1
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10186081

## Citation

> US National Institutes of Health, RePORTER application 10186081, Peripheral vestibular hypofunction and neurosensory coding (1R01DC019459-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10186081. Licensed CC0.

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