# Functional development of interneurons that mediate the vestibulo-ocular reflex

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $371,625

## Abstract

Project Summary / Abstract of Supplemental Research
The vestibular system is critical for maintaining stable gaze. The simple, well­understood system responsible
for stable gaze has served as a means to understand fundamental principles of neural circuits. The parent R01
focuses on using the vestibulo­ocular reflex system of the larval zebrafish as a simple and tractable model to
determine the origin of cues that specify vestibular interneuron identity. Completion of the parent R01 stands to
make a significant contribution: to reveal the principles responsible for balance circuit development. Therefore
the parent work is a major step towards the long­term goal of using such an understanding to shed light on the
mechanisms underlying vestibular and neurodevelopmental dysfunction.
Together with our collaborator, we have validated a new transgenic reagent that allows us to selectively express
human 4R­Tau in vestibular brainstem neurons. We have observed pronounced postural and balance defects
in these fish, motivating us to apply for supplemental funding. We propose to supplement our R01 by examining
the behavioral and molecular consequences of human 4R­Tau protein on the vestibulo­ocular reflex circuit. We
will compare vestibulo­ocular reflex behavior longitudinally in fish that do / do not express human 4R­Tau pro­
tein in neurons responsible for gaze stabilization. Next, we will compare the transcriptional profiles of neurons
from fish that do / do not express human 4R­Tau protein in central vestibular neurons. First, we will assay the
vestibular neurons themselves, and then, to understand the circuit­level consequences of 4R­Tau expression,
we will compare the downstream population of extraocular motor neurons. Our work will serve to evaluate the
suitability of the zebrafish gaze­stabilization system as a means to evaluate the basic behavioral and molecu­
lar mechanisms of human 4R­Tau expression. As Tau protein is closely linked to Alzheimer’s disease and its
related dementias (e.g. progressive supranuclear palsy), our work is an important step towards understanding
these debilitating disorders.

## Key facts

- **NIH application ID:** 10499079
- **Project number:** 3R01DC017489-04S1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** David Schoppik
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $371,625
- **Award type:** 3
- **Project period:** 2018-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499079

## Citation

> US National Institutes of Health, RePORTER application 10499079, Functional development of interneurons that mediate the vestibulo-ocular reflex (3R01DC017489-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499079. Licensed CC0.

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