# Administrative Supplement for Molecular Mechanisms of Hair Bundle Development and Maintenance

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2022 · $373,375

## Abstract

Project Summary
 The loss of synaptic connectivity in the hippocampus is an early degenerative change that is highly
associated with cognitive decline in Alzheimer’s Disease (AD) patients. Current FDA-approved treatments for
AD are limited to targeting late-stage formation of amyloid beta plaques and do not address the earlier
synaptopathy that contributes to cognitive decline. There is thus a significant unmet need for
pharmacotherapeutics to maintain synaptic connectivity, or to stimulate synaptogenesis in aging brains, as an
approach to ameliorate AD progression in patients. The actin cytoskeleton is the main structural scaffold
determining post-synaptic spine architecture and formation of new spines. Based upon our preliminary data,
we hypothesize that a myosin molecular motor is a critical component of the post-synaptic density that
remodels the actin cytoskeleton to alter synaptic architecture. Our hypothesis is based upon multiple lines of
preliminary evidence and builds upon the function of myosin motors controlling the actin cytoskeleton in other
systems. The goal of this supplemental project is to perform a pilot study testing the hypothesis that
manipulating myosin activity can control hippocampal synaptogenesis and plasticity in aging brains. In Aim 1,
we will localize specific myosin proteins and their normal expression in hippocampal sub-regions, as well
identify changes in synaptic structure resulting from their genetic ablation. In Aim 2, we will use
electrophysiology and behavioral assays in mice to assess functional changes in response to loss of specific
myosin proteins. If successful, this project will provide critical pre-clinical efficacy data for the development of
myosin agonists / antagonists as potential pharmacotherapeutics for the treatment cognitive decline in AD.

## Key facts

- **NIH application ID:** 10498178
- **Project number:** 3R01DC018827-02S1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Jonathan Edward Bird
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $373,375
- **Award type:** 3
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10498178

## Citation

> US National Institutes of Health, RePORTER application 10498178, Administrative Supplement for Molecular Mechanisms of Hair Bundle Development and Maintenance (3R01DC018827-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10498178. Licensed CC0.

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