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The Journal of Neuroscience, November 1, 2000, 20(21):8138-8143

The Circadian Clock Mutation Alters Sleep Homeostasis in the Mouse

Erik Naylor^{1, 2}, Bernard M. Bergmann⁵, Kristyn Krauski¹, Phyllis C. Zee^{1, 2, 4}, Joseph S. Takahashi^{1, 2, 3, 4}, Martha Hotz Vitaterna^{1, 2}, and Fred W. Turek^{1, 2, 4}

¹ Department of Neurobiology and Physiology, ² Center for Circadian Biology and Medicine, and ³ Howard Hughes Medical Institute, Northwestern University, Evanston, Illinois 60208, ⁴ Department of Neurology, Northwestern University Medical School, Chicago, Illinois 60611, and ⁵ Sleep Research Laboratory, Department of Psychiatry, University of Chicago, Chicago, Illinois 60637

The onset and duration of sleep are thought to be primarily under the control of a homeostatic mechanism affected by previous periods of wake and sleep and a circadian timing mechanism that partitions wake and sleep into different portions of the day and night. The mouse Clock mutation induces pronounced changes in overall circadian organization. We sought to determine whether this genetic disruption of circadian timing would affect sleep homeostasis. The Clock mutation affected a number of sleep parameters during entrainment to a 12 hr light/dark (LD 12:12) cycle, when animals were free-running in constant darkness (DD), and during recovery from 6 hr of sleep deprivation in LD 12:12. In particular, in LD 12:12, heterozygous and homozygous Clock mutants slept, respectively, ~1 and ~2 hr less than wild-type mice, and they had 25 and 51% smaller increases in rapid eye movement (REM) sleep during 24 hr recovery, respectively, than wild-type mice. The effects of the mutation on sleep are not readily attributable to differential entrainment to LD 12:12 because the baseline sleep differences between genotypes were also present when animals were free-running in DD. These results indicate that genetic alterations of the circadian clock system and/or its regulatory genes are likely to have widespread effects on a variety of sleep and wake parameters, including the homeostatic regulation of sleep.

Key words: circadian; sleep; Clock mutation; gene; REM; NREM delta power; sleep homeostasis

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20218138-06$05.00/0

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