title: Homeostatic and circadian contribution to EEG and molecular state variables of sleep regulation.
abstract: OBJECTIVE
  Besides their well-established role in circadian rhythms, our findings that the forebrain expression of the clock-genes Per2 and Dbp increases and decreases, respectively, in relation to time spent awake suggest they also play a role in the homeostatic aspect of sleep regulation. Here, we determined whether time of day modulates the effects of elevated sleep pressure on clock-gene expression. Time of day effects were assessed also for recognized electrophysiological (EEG delta power) and molecular (Homer1a) markers of sleep homeostasis.
  
  
  METHODS
  EEG and qPCR data were obtained for baseline and recovery from 6-h sleep deprivation starting at ZT0, -6, -12, or -18.
  
  
  METHODS
  Mouse sleep laboratory.
  
  
  METHODS
  Male mice.
  
  
  METHODS
  Sleep deprivation.
  
  
  RESULTS
  The sleep-deprivation induced changes in Per2 and Dbp expression importantly varied with time of day, such that Per2 could even decrease during sleep deprivations occurring at the decreasing phase in baseline. Dbp showed similar, albeit opposite dynamics. These unexpected results could be reliably predicted assuming that these transcripts behave according to a driven damped harmonic oscillator. As expected, the sleep-wake distribution accounted for a large degree of the changes in EEG delta power and Homer1a. Nevertheless, the sleep deprivation-induced increase in delta power varied also with time of day with higher than expected levels when recovery sleep started at dark onset.
  
  
  CONCLUSIONS
  Per2 and delta power are widely used as exclusive state variables of the circadian and homeostatic process, respectively. Our findings demonstrate a considerable cross-talk between these two processes. As Per2 in the brain responds to both sleep loss and time of day, this molecule is well positioned to keep track of and to anticipate homeostatic sleep need.
  
  
  BACKGROUND
  Curie T; Mongrain V; Dorsaz S; Mang GM; Emmenegger Y; Franken P. Homeostatic and circadian contribution to EEG and molecular state variables of sleep regulation. SLEEP 2013;36(3):311-323.
authors: Center for Integrative Genomics, University of Lausanne, Switzerland.
authors: Thomas
authors: T
authors: Curie
authors: Valérie
authors: V
authors: Mongrain
authors: Stéphane
authors: S
authors: Dorsaz
authors: Géraldine M
authors: GM
authors: Mang
authors: Yann
authors: Y
authors: Emmenegger
authors: Paul
authors: P
authors: Franken
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods*; D015870:Gene Expression / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D000072233:Homer Scaffolding Proteins; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D056950:Period Circadian Proteins / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C498260:Dbp protein, mouse; D000072233:Homer Scaffolding Proteins; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D014157:Transcription Factors
keywords: Circadian rhythms; clock genes; simulation model; sleep deprivation; sleep homeostasis