Sleep is an evolutionarily conserved behavior that is important for neural performance and function, yet the genes and neurons that regulate sleep are poorly understood. The best-characterized sleep regulators are the hypocretin neuropeptides, which promote wakefulness and inhibit sleep. Loss of hypocretin neurons causes narcolepsy, an incurable neurological disorder characterized by excessive daytime sleepiness and fragmented sleep/wake states. Hypocretin neurons thus play a critical role in regulating sleep, but virtually nothing is known about factors that regulate their specification. Preliminary studies in the zebrafish, Danio rerio, have identified 19 genes with enriched expression in hypocretin neurons. I will test the hypothesis that some of these genes are necessary and/or sufficient to specify the hypocretin neuronal fate. Identifying such factors will greatly expand our understanding of hypocretin neuronal development, and may elucidate how these neurons are assembled into a functional sleep circuit. Ultimately, these experiments could lead to novel therapies that prevent or reverse the loss of hypocretin neurons in patients with narcolepsy.

Public Health Relevance

Hypocretin neuropeptides play an evolutionarily conserved role in promoting wakefulness and inhibiting sleep. The loss of hypocretin neurons causes the sleep disorder narcolepsy, which has no known cure and is treated symptomatically. Using zebrafish as a simple vertebrate model, I will investigate the genetic basis of hypocretin neuronal development, which will improve our understanding of how sleep regulatory circuits are established and may lead to long-term, cellular therapies for narcolepsy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS077844-02
Application #
8527544
Study Section
Special Emphasis Panel (ZRG1-F03A-N (20))
Program Officer
He, Janet
Project Start
2012-08-01
Project End
2014-10-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$42,232
Indirect Cost
Name
California Institute of Technology
Department
None
Type
Schools of Arts and Sciences
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125