When we fall asleep, the world around us doesn't stop producing stimuli. Preparing for sleep, most animals seek out a secluded spot that not only protects them from predators, but also helps filter out some of the sensory information that is constantly bombarding our senses. In addition to this behavioral filtering, the brain itself filters information during sleep. We propose that by studying how sensory information is gated during sleep, we can gain insight into how sensory awareness is generated in the brain. We are establishing novel experimental platforms that exploit the dynamic arousal threshold during sleep in Drosophila melanogaster, a powerful model for the genetic dissection of nervous system function. We will look for genes and neurons that gate sensory information during sleep. Sleep in Drosophila displays many characteristics of mammalian sleep, and known sleep factors are conserved between flies and us. We will use the fly to understand another puzzle that interests us - how animals regulate their sleep amount. We are all familiar with the drowsy feeling that results from inadequate sleep, when all we want to do is crawl back to bed. The need for sleep can be overwhelming, and this is due to the essential nature of this behavior. But what is this feeling, where does it come from? Despite longstanding interest in this question, we do not have any mechanistic insights into how sleep homeostasis ? the physiological balance between waking and sleep - is regulated. Using the same system we designed to probe arousal threshold, we can deprive flies of sleep in a high-throughput and automated manner, and look for animals whose rebound sleep deviates from normal. Our approach is particularly innovative in using the same system to study two distinct but essential biological questions. Finding animals that do not sense the loss of sleep, or cannot respond adequately, will afford an opportunity to study molecular and neural correlates of sleep homeostasis. This is of great relevance for human health, as sleep disturbances underlie many significant health problems including depression, diabetes and cancer.

Public Health Relevance

Sleep disorders are common in the general population, with almost one hundred sleep disorders described to date (e.g. sleep apnea, narcolepsy, advanced and delayed sleep phase syndromes), making it imperative to understand this behavior in order to alleviate sleep-related health problems. The fly has been at the vanguard of efforts to understand many previously mysterious biological phenomena and there is every reason to believe that this role will be revisited in investigating the molecular mechanisms of sleep regulation. For instance, factors that are linked to familial sleep disorders in humans ? Period and Casein Kinase 1- had their homologues discovered and first characterized in Drosophila.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
NIH Director’s New Innovator Awards (DP2)
Project #
1DP2AT009498-01
Application #
9165436
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mudd, Lanay Marie
Project Start
2016-09-30
Project End
2021-09-29
Budget Start
2016-09-30
Budget End
2021-09-29
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Harvard Medical School
Department
Biology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115