# The Peripheral Vestibular System in Congenital Vestibular Disorders

> **NIH NIH R01** · GEORGE WASHINGTON UNIVERSITY · 2021 · $325,292

## Abstract

ABSTRACT
In the US, an estimated 3.3 million children experience dizziness and balance problems (19). Children with
congenital vestibular disorders (CVDs) show delayed motor development and challenges in maintaining posture
and balance, indicating that the vestibular neural circuitry is affected. Computed tomography (CT) shows that
children with CVDs most commonly form a sac-like inner ear with the semicircular canals missing or truncated.
It is not known how their vestibular connectivity is altered. We hypothesize that formation of a sac-like inner ear
during early gestation results in a reduced number of vestibular ganglion cells forming fewer primary vestibular
synapses on hair cells peripherally and on vestibular nuclei neurons centrally, leading to underconnectivity in the
vestibular system. We further hypothesize that the sac-like inner ear pathology results in abnormal convergence
of canal and otolith fibers onto vestibular nuclei neurons, or anomalous connectivity, contributing to abnormal
signal processing in these neurons. The proposed work will establish a framework to test the overarching
hypothesis that formation of a congenitally-malformed, sac-like inner ear alters the peripheral and
central vestibular neural circuitry. To address these questions, our laboratory has implemented and validated
a new chick embryo model. We can produce a reproducible animal model in 85% of cases by surgically rotating
the developing inner ear or “otocyst” 180° on one side in two-day old chick embryos (E2). Since the procedure
involves Anterior-posterior axis Rotation of the Otocyst to produce a Sac-like inner ear, the model is called the
ARO/s chick. The sac-like inner ear of ARO/s chicks resembles the sac-like inner ear in children with CVDs.
After hatching (H), ARO/s chicks experience challenges in maintaining balance and walking. As a first step in
understanding the consequences of the sac-like inner ear on the developing vestibular neural circuitry, in
Specific Aim 1 we will further analyze the vestibular epithelium and quantify vestibular ganglion cells to
determine to what extent primary vestibular afferent synapses are decreased in ARO/s chicks. In Specific Aim
2, we will combine imaging and electrophysiological approaches to determine whether a structurally-uniform
class of vestibular nuclei neurons, the principal cells of the tangential nucleus (TN), acquire the orderly inputs
from canal and otolith fibers, passive and active membrane properties, and synaptic transmission found in normal
chicks. In Specific Aim 3, we will perform ethological tests to characterize posture and balance in H5 ARO/s
chicks, followed by the horizontal vestibuloocular reflex (hVOR) using Earth vertical axis rotation (EVAR) to test
canal function and the static tilting platform test to evaluate otolith function. The experimental outcomes will
provide a foundation to better understand the pathological changes occurring in the vestibular neural circuitry of
CVD patients...

## Key facts

- **NIH application ID:** 10183006
- **Project number:** 1R01DC019369-01
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Kenna D Peusner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $325,292
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10183006

## Citation

> US National Institutes of Health, RePORTER application 10183006, The Peripheral Vestibular System in Congenital Vestibular Disorders (1R01DC019369-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10183006. Licensed CC0.

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