The overall objectives of the proposed experiments in this application are to develop the mouse as an animal model for elucidating the genetic and molecular mechanisms for sleep regulation and to tet specific hypotheses regarding the importance of the genetic background and physiological state of both male and female mice in the regulation of sleep as well as the effects of stress on sleep. Stress can have major disruptive effects on sleep as well as the circadian clock, which itself plays a fundamental role in the regulation of sleep. Both genetic and environmental factors contribute to the regulation of sleep as well as to how the sleep and circadian clock systems of any one individual will be affected by stress. In the proposed studies, the effects in mice of acute stress, chronic mild stress, and short- term sleep deprivation on sleep and circadian rhythms will be determined. Mice with genetic differences will be studied. These genetic differences will be polygenic for some studies, or will test the roles of single candidate genes in others. In view of gender differences in both sleep and the response to stress that have been observed in other species, primarily in humans, the proposed studies will include females in different stages of the estrous cycle and after the age-related loss in cyclicity. An additional objective of this proposal is to develop and validate the use of a novel automated sleep analysis system in the mouse. It is anticipated that these studies will contribute to an understanding of the mechanisms whereby stress impacts sleep regulation. The results of these studies also will form a critical basis for use of the tools of mouse genetics to identify genetic and physiological factors which may influence sleep disruption. Such information is likely ultimately to lead to more effective interventions for humans who suffer from sleep disturbances due to stress or related factors, and may lead to new treatments for mental and physical disorders associated with sleep-wage abnormalities.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Special Emphasis Panel (ZHL1-CSR-R (S1))
Program Officer
Monjan, Andrew A
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Northwestern University at Chicago
Schools of Arts and Sciences
United States
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Turek, Fred W; Vitaterna, Martha Hotz (2011) Molecular neurobiology of circadian rhythms. Handb Clin Neurol 99:951-61
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Paul, Ketema N; Laposky, Aaron D; Turek, Fred W (2009) Reproductive hormone replacement alters sleep in mice. Neurosci Lett 463:239-43
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Kolker, Daniel E; Vitaterna, Martha Hotz; Fruechte, Ethan M et al. (2004) Effects of age on circadian rhythms are similar in wild-type and heterozygous Clock mutant mice. Neurobiol Aging 25:517-23
Meerlo, Peter; Westerveld, Peter; Turek, Fred W et al. (2004) Effects of gamma-hydroxybutyrate (GHB) on vigilance states and EEG in mice. Sleep 27:899-904
Koehl, Muriel; Battle, Sally E; Turek, Fred W (2003) Sleep in female mice: a strain comparison across the estrous cycle. Sleep 26:267-72

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