# Synaptic Processing in the vestibular system

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $165,266

## Abstract

COMPUTATIONAL MODELING OF ION TRANSPORT AND ENERGY DEPLETION AT VESTIBULAR
 SYNAPSES: RELEVANCE TO ALZHEIMER’S DISEASE
Project Summary
In our parent award, “Synaptic Processing in the Vestibular System,“ our goal is to develop computational
models of how the distribution of ion channels and transporters contributes to afferent firing at the type I
vestibular hair cell synapse. Specifically, we are investigating the roles of quantal and non-quantal
transmission at this unique synapse. Recent research from various types of studies indicates links
between the proper function of the vestibular system and Alzheimer's disease. Of particular interest is
research that suggests that falls precede detectable cognitive changes in Alzheimer's patients. Such
studies point to the possibility that changes at the vestibular periphery could be an early and undetectable
event that disrupts normal synaptic transmission. As the vestibular afferents project to the hippocampus,
it is reasonable to hypothesize that reduced synaptic input may contribute to the development of
Alzheimer's and other neurodegenerative diseases. This hypothesis forms the fundamental
motivation for this supplement proposal. Indeed, much research indicates that Alzheimer's disease is
linked to energetic depletion, aberrant functions of ion channels, and disorders of ion homeostasis. Here
we propose to extend our current biophysical model of the vestibular-hair cell calyx synapse n several
ways, including through the inclusion of a more complete model of the Na/K pump that permits us to
model energetic depletion and through the inclusion of recent data on membrane transporter and ion
channel changes associated with Alzheimer's disease. This effort will increase our understanding of the
vestibular periphery within the scope of the original grant, and also be highly relevant to Alzheimer's
disease and related dementias in which ion channel changes are implicated. The innovation and
significance of this research is that our approach of computational modeling of membrane transport does
not appear to have been applied to aid in the understanding of the biophysical basis of Alzheimer's
disease. Computational models help to unify disparate data and can aid in in silico drug discovery efforts,
which are urgently needed given the increasing percentage of the population that are at risk for
neurodegenerative diseases.

## Key facts

- **NIH application ID:** 10123951
- **Project number:** 3R01DC012347-08S1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Ruth Anne Eatock
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $165,266
- **Award type:** 3
- **Project period:** 2020-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123951

## Citation

> US National Institutes of Health, RePORTER application 10123951, Synaptic Processing in the vestibular system (3R01DC012347-08S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10123951. Licensed CC0.

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