Sleep is an essential biological process that is conserved from flies to humans. Studies of sleep regulation have focused on two main mechanisms: the circadian mechanism that controls when to sleep and the homeostatic mechanism that regulates how much to sleep. Nevertheless, other factors, such as gender, also affect sleep, but the mechanism underlying gender-dimorphic sleep regulation is poorly understood. This proposal aims to investigate a novel Drosophila neural circuit involved in male-specific regulation of sleep. We recently identified a small number of neurons in the brain whose activation leads to markedly reduced sleep in male flies, but not in female flies. This is exciting because although several sleep-regulatory neuronal centers have been identified in Drosophila, this is the first example of a gender-dimorphic arousal center. Our preliminary data suggest that the newly identified arousal center promotes wakefulness in the presence of females and makes synaptic contacts with neurons that express the male-specific transcription factor FruitlessM, which is required for male courtship behavior. To understand how this novel arousal center regulates sleep in a gender-dimorphic manner, several key questions need to be addressed. What are the input signals and behavioral outputs of this neural center? What other neuronal populations does the neural center connect to and which neurotransmission system does it employ? We will address these questions using an array of genetic tools that are available for circuit analysis in Drosophila. This work will investigate a novel neural circuit involved in male-specific regulation of sleep and will produce new research avenues for understanding sex differences in sleep. Further, this work may provide valuable insights into the fundamental problem of how the brain balances competing needs to decide on appropriate behaviors.

Public Health Relevance

Sleep disorders are especially prevalent among neurological patients and impinge on quality of life of both patients and their caregivers. Several factors, including gender, affect sleep. The proposed studies will elucidate the neural mechanisms of gender-dimorphic regulation of sleep and may lead to novel approaches to treat sleep disorders that account for gender differences in this essential biological process.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS094782-02
Application #
9127364
Study Section
Neuroendocrinology, Neuroimmunology, Rhythms and Sleep Study Section (NNRS)
Program Officer
He, Janet
Project Start
2015-09-01
Project End
2017-08-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Machado, Daniel R; Afonso, Dinis Js; Kenny, Alexandra R et al. (2017) Identification of octopaminergic neurons that modulate sleep suppression by male sex drive. Elife 6: