The circadian Clock mutation alters sleep homeostasis in the mouse

The onset and duration of sleep are thought to be primarily under the contr ol of a homeostatic mechanism affected by previous periods of wake and slee p and a circadian timing mechanism that partitions wake and sleep into diff erent portions of the day and night. The mouse Clock mutation induces prono unced changes in overall circadian organization. We sought to determine whe ther this genetic disruption of circadian timing would affect sleep homeost asis. The Clock mutation affected a number of sleep parameters during entra inment to a 12 hr light/dark (LD 12: 12) cycle, when animals were free-runn ing in constant darkness (DD), and during recovery from 6 hr of sleep depri vation in LD 12: 12. In particular, in LD 12: 12, heterozygous and homozygo us Clock mutants slept, respectively, similar to1 and similar to2 hr less t han 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 mi ce. The effects of the mutation on sleep are not readily attributable to di fferential entrainment to LD 12: 12 because the baseline sleep differences between genotypes were also present when animals were free-running in DD. T hese results indicate that genetic alterations of the circadian clock syste m and/or its regulatory genes are likely to have widespread effects on a va riety of sleep and wake parameters, including the homeostatic regulation of sleep.