# Investigation of Neuropeptide Signaling Mechanisms that Control Sleep

> **NIH NIH R15** · SKIDMORE COLLEGE · 2022 · $427,433

## Abstract

Sleep disturbances are increasingly common and are associated with a variety of comorbidities and other public
health consequences. It is therefore critical to improve our understanding of the neural mechanisms that control
the timing and quality of sleep. Key signaling molecules that regulate sleep in animals ranging from flies to
humans come from the family of neuropeptide transmitters. These molecules have sparse expression levels and
selective effects on behavior, including sleep, making them prime candidates for the development of focused
drug treatments with minimal side effects. However, the mechanisms by which these molecules act individually
and in concert to regulate target cells in the brain and thus behavior are poorly understood. This renewal
application will take advantage of the powerful genetics and relatively simple sleep network organization of the
fruit fly, Drosophila melanogaster, to address how neuropeptides function at the molecular, cellular, and
behavioral levels to regulate sleep. In Aim 1, we will utilize optogenetic activation of specific subsets of neurons
expressing the sleep-promoting transmitter short neuropeptide F (sNPF) in order to determine their particular
roles in sleep regulation. In Aim 2, we will coactivate sleep-promoting sNPF neurons and wake-promoting
neurons to determine their hierarchical organization in sleep regulation. In Aim 3, we will utilize live fluorescent
imaging to test the hypothesis that sNPF acts as an inhibitory output signal onto leucokinin neurons that regulate
sleep. In combination, the proposed work will allow us to establish how sNPF neurons function within sleep
regulatory networks in the brain, expanding our understanding of the mechanisms that control sleep and
wakefulness at the molecular and circuit levels. In turn, this knowledge will provide a basis for the design of more
effective treatments of human sleep abnormalities. This R15 AREA renewal proposal will directly involve
undergraduate students in all aspects of the research, including designing and carrying out studies involving
techniques of genetic manipulation, molecular and cellular neurobiology, and behavioral analysis. Students will
also take an active role in disseminating the scientific knowledge acquired through their research, in the form of
conference presentations and published manuscripts. Their experiences will provide formative training for future
careers in biomedical fields.

## Key facts

- **NIH application ID:** 10359989
- **Project number:** 2R15NS101692-02A1
- **Recipient organization:** SKIDMORE COLLEGE
- **Principal Investigator:** Christopher George Lorenz Vecsey
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $427,433
- **Award type:** 2
- **Project period:** 2021-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359989

## Citation

> US National Institutes of Health, RePORTER application 10359989, Investigation of Neuropeptide Signaling Mechanisms that Control Sleep (2R15NS101692-02A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10359989. Licensed CC0.

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