# Synaptic signals that drive the long-term maintenance of homeostatic neuroplasticity

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2020 · $266,875

## Abstract

PROJECT SUMMARY
Background and Objectives: Synapses and circuits possess a robust capacity for stress response.
They employ homeostatic regulatory mechanisms to maintain physiologically appropriate levels of
synaptic output. Improved knowledge about homeostatic forms of synaptic plasticity should lead to a
better understanding of neurological disorders that occur when synapse stability is lost. Using genetic
and electrophysiological approaches at the model Drosophila neuromuscular junction (NMJ) synapse,
three new factors required for the long-term homeostatic maintenance of NMJ function were uncov-
ered: two tyrosine kinase signaling molecules residing in the muscle and one phospholipase C-β
(PLCβ) molecule residing in the neuron. The objective of this proposal is to understand how these
three molecules integrate cell-cell signaling processes to maintain synapse stability throughout life.
Specific Aims and Research Design: This project has three specific aims. The first two aims will
delineate how each respective tyrosine kinase drives a muscle-to-nerve signaling process to stabilize
synaptic activity over long periods of developmental time. The third aim will address how neuronal
PLCβ integrates cell-cell signals at the synapse to autonomously control neuronal output. Each aim
will combine electrophysiology, genetics, pharmacology, biochemistry, and synapse imaging. A prima-
ry assay for each aim will be to challenge NMJ function – usually by inhibiting glutamate receptors in
the muscle – and then to examine the NMJ by electrophysiology to check if it appropriately responds
to that challenge by releasing more glutamate from the neuron. By combining this electrophysiological
approach with synapse imaging it will be possible to identify manipulations that specifically impair
synapse function – as opposed to other parameters, like synapse growth. The expected outcome is a
detailed model of how synaptic tissues transmit cell-cell signals to maintain stable activity levels.
Health Relatedness: Neurological disorders like epilepsy, ataxia, and migraine are associated with
unstable neuronal function. Therefore, understanding how synapses work to maintain stability on a
molecular level could have profound implications for disorders with underlying neuronal instabilities.
Yet the cell-cell signaling events that tightly control levels of synaptic output are poorly understood.
The genetically tractable Drosophila NMJ employs homoestatic strategies to stabilize synapse
function – such as altering levels of presynaptic calcium influx – that are shared by mammalian central
synapses. Taking advantage of the molecular and genetic tools offered by the NMJ promises to shed
light on universally conserved mechanisms of how synapses maintain stable function throughout life.

## Key facts

- **NIH application ID:** 9829589
- **Project number:** 5R01NS085164-04
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** CARL ANDREW FRANK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $266,875
- **Award type:** 5
- **Project period:** 2016-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9829589

## Citation

> US National Institutes of Health, RePORTER application 9829589, Synaptic signals that drive the long-term maintenance of homeostatic neuroplasticity (5R01NS085164-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9829589. Licensed CC0.

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