# Acetylcholinergic Neurotransmission During Aging

> **NIH NIH K01** · DELAWARE STATE UNIVERSITY · 2022 · $92,952

## Abstract

Project Summary
This proposal is aimed at determining the role of changes in acetylcholinergic neurotransmission on synaptic
physiology and behavior during aging. Acetylcholine regulation has long been thought to play a crucial role in
the mediation of cognitive and behavioral function as an organism ages, yet the precise function of acetylcholine
in this process has, till date remained poorly elucidated. We are using a subtle mutation in the vesicular
acetylcholine transporter (VAChT) the protein responsible for the packaging of ACh for exocytotic release to
determine the role of cholinergic neurotransmission during aging. The short life span of the fly coupled, with
additional genetic tools unique to this system will allow us to assess the impact of altered ACh release on
behavior and synaptic physiology throughout the lifespan of the animal. Our preliminary data show for the first
time action potential firing in aged Drosophila cholinergic neurons; we also show that Vacht mutations have a
differential effect on organismal survival with the most severe mutation have a significantly shorter lifespan than
wildtype. These and other results have allowed us to advance the central hypothesis that a decrease in
VAChT function produce a corresponding decrease in neuronal excitability and behavior that are
amplified with age In Aim 1, we will determine the effect of a relatively mild reduction decrease in VAChT
function on synaptic physiology at central cholinergic synapses during aging. In Aim 2, we will measure whether
the reduction in Vacht affects cognition at defined points across the lifespan. Future studies will be aimed at
using the system that we have developed here to understand the mechanisms behind the preferential
susceptibility of cholinergic neurons in pathological conditions such as Alzheimer’s disease.

## Key facts

- **NIH application ID:** 10600238
- **Project number:** 3K01AG049055-05S1
- **Recipient organization:** DELAWARE STATE UNIVERSITY
- **Principal Investigator:** Hakeem O Lawal
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $92,952
- **Award type:** 3
- **Project period:** 2015-09-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10600238

## Citation

> US National Institutes of Health, RePORTER application 10600238, Acetylcholinergic Neurotransmission During Aging (3K01AG049055-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10600238. Licensed CC0.

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