Sleep disturbances are increasingly common and are associated with a variety of comorbidities and other public health consequences. It is therefore critical to improve our understanding of the neural mechanisms that control the timing and quality of sleep. Key signaling molecules that regulate sleep in animals ranging from flies to humans come from the family of neuropeptide transmitters. These molecules have sparse expression levels and selective effects on behavior, including sleep, making them prime candidates for the development of focused drug treatments with minimal side effects. However, the mechanisms by which these molecules act individually and in concert to regulate target cells in the brain and thus behavior are poorly understood. This proposal will take advantage of the powerful genetics and relatively simple sleep network organization of the fruit fly, Drosophila melanogaster, to address how neuropeptides function at the molecular, cellular, and behavioral levels to regulate sleep.
In Aim 1, we will perform live fluorescent imaging to identify cellular targets and intracellular signaling mechanisms downstream of the receptor for the newly described sleep regulator, neuropeptide F (NPF), and determine how this molecule interacts with two additional established sleep regulators, short neuropeptide F (sNPF) and pigment dispersing factor (PDF).
In Aim 2, we will carry out optogenetic activation of neuronal populations producing these same neuropeptides either individually or in combination, and record the effects on sleep behavior. In combination, the proposed work will allow us to establish the causal roles of key neuropeptide signaling molecules in the control of sleep, expanding our understanding of the mechanisms that control sleep and wakefulness at the molecular and circuit levels. In turn, this knowledge will provide a basis for the design of more effective treatments of human sleep abnormalities. This R15 AREA proposal will directly involve undergraduate students in all aspects of the research, including designing experiments, carrying out studies involving techniques of genetic manipulation, molecular and cellular neurobiology, and behavioral analysis. Their experiences will provide formative training for future careers in biomedical fields.

Public Health Relevance

Sleep abnormalities have widespread and costly public health consequences, yet we have only a rudimentary understanding of the events occurring at the cellular level in the brain that regulate sleep. This proposal will address how certain brain signaling molecules called neuropeptides act at the cellular level to control sleep behavior. The findings of these studies will provide a more complete understanding of the nature and regulation of sleep, which will allow for the development of more effective treatments of prevalent and widely disruptive sleep abnormalities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15NS101692-01A1
Application #
9516503
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
He, Janet
Project Start
2018-02-01
Project End
2021-01-31
Budget Start
2018-02-01
Budget End
2021-01-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Skidmore College
Department
Neurosciences
Type
Schools of Arts and Sciences
DUNS #
020670741
City
Saratoga Springs
State
NY
Country
United States
Zip Code
12866