# Mechanism and function of presynaptic inhibition in Drosophila proprioceptors

> **NIH NIH F32** · UNIVERSITY OF WASHINGTON · 2021 · $34,281

## Abstract

PROJECT SUMMARY / ABSTRACT
Interaction with the external environment is made possible by sensory systems, which transduce physical,
chemical, or visual information into electrical signals that the brain can encode and interpret. Once transduced
into electrical signals, environmental stimuli are subject to filtering to enhance or diminish specific features and
to prevent overstimulation. Presynaptic inhibition is a ubiquitous feature of early sensory processing and is
imperative for modulating synaptic output from sensory neurons to central neurons. The inhibitory
neurotransmitter GABA is released onto sensory afferents, depolarizes the axon terminal, and suppresses
neurotransmitter release. Despite the importance and prevalence of presynaptic inhibition, it is not clear how
depolarization of the axon terminal results in synaptic inhibition. In addition, the GABAergic interneurons
providing synaptic input to the afferent terminals remain elusive and therefore their function and regulation are
unknown. In order to understand presynaptic inhibition and its role in sensory encoding, I propose to use
Drosophila leg proprioceptors as a model system. Across animals from humans to insects, proprioceptors
located throughout the body project to the central nervous system, where information such as limb movement
or position are encoded. By investigating the mechanism and regulation of presynaptic inhibition in Drosophila,
I will benefit from the relatively simplified circuitry of their nervous system and the unparalleled ability to
genetically target subpopulations of neurons. I will perform experiments to address three specific questions: 1)
what is the biophysical mechanism of presynaptic inhibition in proprioceptors and 2) do GABAergic
interneurons have target specificity for specific proprioceptors, and 3) how are proprioceptors dynamically
regulated during spontaneous and passive movement? To address the first question, I will use voltage imaging
to measure membrane voltage of proprioceptors during induced inhibition by stimulating with exogenous
GABA. Then, I will determine whether GABAergic interneurons are promiscuous or if they have functionally
segregated targets. Lastly, I will determine which GABAergic interneurons are activated by direction-sensitive
or movement-sensitive proprioceptors. By measuring membrane voltage across proprioceptors during GABA
application, active movements, and passive movements, I hope to identify the biophysical mechanism of
presynaptic inhibition and determine how the inhibitory neurons are dynamically recruited to provide feedback.

## Key facts

- **NIH application ID:** 10380469
- **Project number:** 3F32NS114150-02S1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Lylah Deady
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $34,281
- **Award type:** 3
- **Project period:** 2021-09-16 → 2022-03-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380469

## Citation

> US National Institutes of Health, RePORTER application 10380469, Mechanism and function of presynaptic inhibition in Drosophila proprioceptors (3F32NS114150-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10380469. Licensed CC0.

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