Homeostatic sleep regulation is preserved in mPer1 and mPer2 mutant mice.
A limited set of genes, Clock, Bmal1, mPer1, mPer2, mCry1 and mCry2, has been shown to be essential for the generation of circadian rhythms in mammals. It has been recently suggested that circadian genes might be involved in sleep regulation. We investigated the role of mPer1 and mPer2 genes in the homeostatic regulation of sleep by comparing sleep of mice lacking mPER1 (mPer1 mutants) or a functional mPER2 (mPer2 mutants), and wild-type controls (WT) after 6 h of sleep deprivation (SD). Our main result showed that after SD, all mice displayed the typical increase of slow-wave activity (SWA; EEG power density between 0.75 and 4 Hz) in nonREM sleep, reflecting the homeostatic response to SD. This increase was more prominent over the frontal cortex as compared to the occipital cortex. The genotypes did not differ in the effect of SD on the occipital EEG, while the effect on the frontal EEG was initially diminished in both mPer mutants. Differences between the genotypes were seen in the 24-h distribution of sleep, reflecting especially the phase advance of motor activity onset observed in mPer2 mutants. While the daily distribution of sleep was modulated by mPer1 and mPer2 genes, sleep homeostasis reflected by the SWA increase after 6-h SD was preserved in the mPer mutants. The results provide further evidence for the independence of the circadian and the homeostatic components underlying sleep regulation.
Kopp
Caroline
C
Institute of Pharmacology and Toxicology, University of Zürich, Switzerland.
Albrecht
Urs
U
Zheng
Binhai
B
Tobler
Irene
I
D000818:Animals; D001143:Arousal / Q000235:genetics; D018797:Cell Cycle Proteins; D002540:Cerebral Cortex / Q000502:physiology*; D002940:Circadian Rhythm / Q000235:genetics*; D003624:Darkness; D004569:Electroencephalography; D005625:Frontal Lobe / Q000502:physiology; D006706:Homeostasis / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics; D009778:Occipital Lobe / Q000502:physiology; D056950:Period Circadian Proteins; D010775:Photic Stimulation; D012890:Sleep / Q000235:genetics*; D012895:Sleep, REM / Q000235:genetics; D014157:Transcription Factors
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D014157:Transcription Factors