The circadian clock mutation alters sleep homeostasis in the mouse - PubMed (original) (raw)

The circadian clock mutation alters sleep homeostasis in the mouse

E Naylor et al. J Neurosci. 2000.

Abstract

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, approximately 1 and approximately 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.

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Figures

Fig. 1.

Fig. 1.

Percentage of recording time spent in the sleep states for all three genotypes. The four bar groups represent wake, NREM or REM sleep, and the percentage of sleep time spent in REM sleep: a measure of the REM/NREM ratio. A shows sleep during the entire 24 hr LD baseline period, whereas the other graphs further break this baseline period into the 12 hr light period (B) and the 12 hr dark period (C). a–c indicate significant pairwise differences between groups (p < 0.05, Tukey–Kramer post hoc tests).

Fig. 2.

Fig. 2.

Percentage of circadian period spent in various sleep states for wild-type and homozygous Clock mice housed in constant darkness. TST, Total sleep time.

Fig. 3.

Fig. 3.

Response to sleep deprivation. Minutes of sleep per hour during baseline, sleep deprivation (gray bar), and recovery periods for wild-type (A), Clock heterozygous (B), and Clock homozygous (C) mice. Black bars represent times of lights off. For comparison, the baseline sleep amounts have been double-plotted in gray during the recovery period.D, The number of additional minutes of sleep over each animal's equivalent baseline for the entire 24 hr LD recovery period.a and b indicate significant pairwise differences between groups (p < 0.05, Tukey–Kramer post hoc tests).

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References

    1. Aeschbach D, Cajochen C, Landolt H, Borbely AA. Homeostatic sleep regulation in habitual short sleepers and long sleepers. Am J Physiol. 1996;270:R41–R53. - PubMed
    1. Akerstedt T, Gillberg M. The circadian variation of experimentally displaced sleep. Sleep. 1981;4:159–169. - PubMed
    1. Andretic R, Chaney S, Hirsh J. Requirement of circadian genes for cocaine sensitization in Drosophila. Science. 1999;285:1066–1068. - PubMed
    1. Antoch MP, Song EJ, Chang AM, Vitaterna MH, Zhao Y, Wilsbacher LD, Sangoram AM, King DP, Pinto LH, Takahashi JS. Functional identification of the mouse circadian Clock gene by transgenic BAC rescue. Cell. 1997;89:655–667. - PMC - PubMed
    1. Benington JH, Heller HC. REM-sleep timing is controlled homeostatically by accumulation of REM- sleep propensity in non-REM sleep. Am J Physiol. 1994;266:R1992–R2000. - PubMed

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