# Maintenance of synapses during adulthood in Drosophila

> **NIH NIH R03** · UNIVERSITY OF OREGON · 2021 · $73,750

## Abstract

PROJECT SUMMARY
The goal of this proposal is to identify genes that regulate an age-dependent change in active zones
(AZs) that causes an age-dependent decline in neuron function. Nearly all organisms, including
humans, decline in function as they age. Nervous systems are particularly vulnerable, as most neurons
appear not to be replaced when damaged. Recent work in Drosophila has identified a molecular
change in aging AZs that causes age-dependent decreases in memory. The conserved AZ component
Bruchpilot (Brp), the fly ortholog of vertebrate ELKS/CAST proteins, increases throughout the brain
during adulthood, resulting in significantly enlarged AZs in older animals. Increasing the lifetime dose of
endogenous Brp results in large AZs and memory deficits in young adults, similar to those in wild-type
old adults, indicating that the age-dependent accumulation of excess Brp at AZs is sufficient to cause
nervous system deficits. Recent evidence indicates that MB neurons provide a signal that regulates Brp
accumulation in other neurons. The nature of this signal and the cell-autonomous mechanisms by
which neurons regulate their accumulation of Brp in response to this signal remain unclear.
Doubling or halving the lifetime dosage of endogenous brp correspondingly accelerates or delays the
age-dependent accumulation of Brp. This suggests that altering the lifetime dosage of regulators of this
process may also either accelerate or delay Brp accumulation. To identify regulators, this application
therefore proposes to: (Aim 1) alter the dosage of conserved genes known to regulate Brp assembly
during development and plasticity and identify those that have effects on age-dependent Brp
accumulation; and (Aim 2) systematically screen a collection of molecularly-defined deletions that span
the Drosophila genome for those that alter age-dependent Brp accumulation and identify the causative
genes.
This work is can be completed in a limited amount of time but is potentially of high impact and an ideal
project in which to engage undergraduate students. The genes identified will form the basis for future
work on understanding the signals and cell-intrinsic mechanisms that cause AZs to change with age.

## Key facts

- **NIH application ID:** 10108714
- **Project number:** 1R03AG070789-01
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** TORY G HERMAN
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $73,750
- **Award type:** 1
- **Project period:** 2021-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10108714

## Citation

> US National Institutes of Health, RePORTER application 10108714, Maintenance of synapses during adulthood in Drosophila (1R03AG070789-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10108714. Licensed CC0.

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