# Modulation of vestibular afferent properties by cholinergic and GABAergic inputs: from neural mechanisms to behavioral outcomes

> **NIH NIH R56** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $338,938

## Abstract

PROJECT SUMMARY
Vestibular receptors encode information about head movements and send these signals through
the vestibular nerve to the brain stem. In turn, receptors and afferents receive bilateral inputs from
cholinergic efferent fibers that originate in the brain stem. To date, the function of the efferent
pathway has remained elusive. It has been suggested that efferents might play a role in normal
development of vestibular reflexes and compensation after lesions. In particular, efferents mainly
affect activity of afferents with calyx terminals that completely cover the basolateral walls of
vestibular hair cells, providing a unique form of synapse. Furthermore, in addition to acetylcholine,
sources for gamma amino butyric acid (GABA) have also been found in the vestibular periphery,
in the supporting cells and probably also in some of the efferent fibers. However, there is little
known about the synaptic properties, receptor types, and interaction between cholinergic and
GABAergic inputs and their effect on responses of vestibular afferents. The goal of the present
proposal is to investigate the underlying mechanisms that mediate changes in afferent response
properties by cholinergic and GABAergic inputs. We will use an in vitro whole preparation of the
vestibular sensory epithelium to study the effect of specific agonists of different subtypes of
receptors on hair cells and afferent terminals in mouse. We will also use an in vivo mouse
preparation to record response properties of vestibular nerve afferents along with optical
stimulation of cholinergic fibers/ GABAergic cells and application of agonists and antagonists of
specific receptors in the inner ear. Finally, we investigate the effect of these drugs on vestibular
function in alert mice by measuring the vestibulo-ocular reflex. Results of these studies provide
the information to correlate changes at the level of single synapses in the end organs, to vestibular
nerve activity, and behavioral responses. The ultimate goal of these studies is to pave the way
for finding new treatment options through local application of drugs into the ear to improve
vestibular compensation in patients.

## Key facts

- **NIH application ID:** 10347515
- **Project number:** 1R56DC019380-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Soroush Sadeghi Ghandehari
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $338,938
- **Award type:** 1
- **Project period:** 2021-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10347515

## Citation

> US National Institutes of Health, RePORTER application 10347515, Modulation of vestibular afferent properties by cholinergic and GABAergic inputs: from neural mechanisms to behavioral outcomes (1R56DC019380-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10347515. Licensed CC0.

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