Continuous sleep loss degrades the physiology of systems throughout the brain and body, eventually causing death. To prevent these consequences, homeostatic mechanisms activate after prolonged waking to promote sleep. Understanding neural mechanisms that control sleep homeostasis will provide insight into the basic functions of sleep and aid the development of interventions that provide resilience to sleep loss, but these circuits have not been clearly characterized. Previous studies have identified a small population of fly neurons that project into the dorsal Fan-shaped Body (dFB) and act as a homeostatic control center for sleep. We have conducted an RNAi screen to identify sleep-promoting dFB input signals and have characterized an output signal released by dFB neurons to induce sleep. In this proposal, we will: (1) use electrophysiology along with receptor RNAis and mutants to confirm dFB input signal identity, (2) create genetic reporters for post-synaptic targets of dFB neurons, and (3) use patch-clamp recordings to test whether dFB excitability is elevated to promote sleep during memory consolidation and degraded in aged flies, resulting in sleep fragmentation.

Public Health Relevance

Consequences of insufficient sleep range from acute cognitive deficits to increased risk of chronic illnesses such as diabetes and hypertension. The proposed project will use a simple model system to understand how sleep control centers detect when the organism requires sleep, then activate to promote sleep. The proposed research is expected to improve our understanding of how sleep is regulated and identify new sleep-promoting interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS105967-02
Application #
9666949
Study Section
Neuroendocrinology, Neuroimmunology, Rhythms and Sleep Study Section (NNRS)
Program Officer
He, Janet
Project Start
2018-04-01
Project End
2023-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Neurosciences
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Omoto, Jaison Jiro; Nguyen, Bao-Chau Minh; Kandimalla, Pratyush et al. (2018) Neuronal Constituents and Putative Interactions Within the Drosophila Ellipsoid Body Neuropil. Front Neural Circuits 12:103
Donlea, Jeffrey M (2018) Roles for sleep in memory: insights from the fly. Curr Opin Neurobiol 54:120-126