Sleep during critical developmental windows is thought to be important for brain maturation. However, examination of a function for sleep in the earliest periods of nervous system development, when neurons are being born, has been limited by the lack of a tractable experimental system. The adult fruit fly is a widely studied model organism for sleep, but the major wave of neurogenesis in Drosophila begins during larval life and ends prior to adulthood. It has remained unknown whether larvae sleep. We present new approaches for long-term monitoring of larval behaviors, leading to identification of a sleep state in Drosophila larvae. We propose exploiting this system to understand how functional coupling of sleep and arousal brain centers changes throughout life. Using real-time behavioral monitoring in a closed-loop sleep deprivation system, we will examine how sleep loss in larvae affects cell division of neural progenitors, and determine the impact of early life sleep loss on adult learning and memory. We will then leverage the larval system to gain new mechanistic insights into how sleep loss is coupled to neurogenesis. Finally, we propose adaptation of our behavioral monitoring device to engineer a scalable system suitable for high-throughput closed-loop manipulation of behavior in larvae and other model organisms. Collectively, this work will generate novel tools and approaches for studying the role of sleep in the developing nervous system.

Public Health Relevance

Sleep during early life plays an important role in refining brain circuitry, but examination of a function for sleep in the earliest periods of brain development has been limited by the lack of a tractable experimental system. The proposed work will establish Drosophila larvae as a platform to study sleep and neurogenesis, opening novel avenues to manipulate and study sleep in the developing brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
NIH Director’s New Innovator Awards (DP2)
Project #
1DP2NS111996-01
Application #
9560092
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
He, Janet
Project Start
2018-09-30
Project End
2023-06-30
Budget Start
2018-09-30
Budget End
2019-06-30
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Psychiatry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104