# Investigating sleep regulation and function during early development

> **NIH NIH R35** · UNIVERSITY OF PENNSYLVANIA · 2024 · $813,596

## Abstract

PROJECT SUMMARY
Sleep characteristics change dramatically across development. In early life, sleep duration and depth are
elevated, and sleep lacks a strong circadian pattern. With maturation, sleep duration tapers to adult levels and
clear sleep rhythms emerge. The genes, molecules, and neural circuits governing developmental changes to
sleep are largely unknown. Sleep in early life is hypothesized to facilitate structural maturation of the brain, and
sleep abnormalities during development may contribute to aberrant neural circuit formation. Moreover, sleep
disorders are highly prevalent in neurodevelopmental disorders (NDDs). Improving sleep by targeting
regulatory pathways may thus represent a new therapeutic avenue in NDDs; however, the knowledge gap
regarding factors controlling early life sleep hinders design of sleep-related strategies. Our research uses the
powerful model system Drosophila to gain novel insights into sleep regulation and function across
developmental periods. Our studies have led to 1) identification of genes that specifically coordinate sleep
maturation, 2) functional insights into the role of sleep during early development, and 3) mechanisms coupling
sleep to NDDs. Building on these efforts, this research program is comprised of three highly integrated
domains that seek to define sleep regulatory mechanisms during development and understand how sleep
influences brain maturation in normal and pathological states. First, in studies spanning larval to adult stages,
we will determine sleep cellular and circuit properties across development. We propose to identify sleep/wake
regulatory neurons of interest in early development, characterize these cells, map connectivity, and
trace/characterize the cells in the adult. Second, we will examine mechanisms controlling emergence of
circadian sleep. Our recent work has pinpointed when sleep rhythms first emerge during Drosophila
development. We will determine mechanisms controlling onset of sleep rhythms, functional consequences of
circadian sleep, and how development of clock-sleep circuits ties into broader sleep regulatory mechanisms.
Third, we propose to utilize genetic screens to investigate molecular/cellular coupling of sleep and NDDs.
Specifically, we will pursue a comprehensive assessment of how NDD-associated gene manipulations affect
sleep across numerous developmental stages, each of which has unique behavioral and molecular features
that might be specifically sensitive to particular perturbations. Genetic findings will be placed into context of
sleep/circadian circuit principles in an ongoing, integrated manner. Collectively, our research program will
generate new insights into the regulation of early life sleep, deepening our understanding of the link between
sleep, brain development, and neurodevelopmental pathology.

## Key facts

- **NIH application ID:** 10886957
- **Project number:** 1R35NS137329-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** MATTHEW S KAYSER
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $813,596
- **Award type:** 1
- **Project period:** 2024-06-01 → 2032-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10886957

## Citation

> US National Institutes of Health, RePORTER application 10886957, Investigating sleep regulation and function during early development (1R35NS137329-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10886957. Licensed CC0.

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