title: Sleep Homeostatic and Waking Behavioral Phenotypes inEgr3-Deficient Mice Associated with Serotonin Receptor 5-HT2Deficits.
abstract: The expression of the immediate early gene early growth response 3 (Egr3) is a functional marker of brain activity including responses to novelty, sustained wakefulness, and sleep. We examined the role of this gene in regulating wakefulness and sleep.
  
  
  
  Electroencephalogram/electromyogram (EEG/EMG) were recorded inEgr3-/- and wild-type (WT) mice during 24 h baseline, 6 h sleep disruption and 6 h recovery. Serotonergic signaling was assessed with 6 h EEG/EMG recordings after injections of nonselective 5-HT2 antagonist (clozapine), selective 5-HT2 antagonists (5-HT2A; MDL100907 and 5-HT2BC; SB206553) and a cocktail of both selective antagonists, administered in a randomized order to each animal.
  
  
  
  Egr3-/- mice did not exhibit abnormalities in the timing of wakefulness and slow wave sleep (SWS); however, EEG dynamics in SWS (suppressed 1-3 Hz power) and in quiet wakefulness (elevated 3-8 Hz and 15-35 Hz power) differed in comparison to WT-mice.Egr3-/- mice showed an exaggerated response to sleep disruption as measured by active wakefulness, but with a blunted increase in homeostatic sleep drive (elevated 1-4 Hz power) relative to WT-mice.Egr3-/-mice exhibit greatly reduced sedative effects of clozapine at the electroencephalographic level. In addition, clozapine induced a previously undescribed dissociated state (low amplitude, low frequency EEG and a stable, low muscle tone) lasting up to 2 h in WT-mice.Egr3-/- mice did not exhibit this phenomenon. Selective 5-HT2A antagonist, alone or in combination with selective 5-HT2BC antagonist, caused EEG slowing coincident with behavioral quiescence in WT-mice but not inEgr3-/- mice.
  
  
  
  Egr3has an essential role in regulating cortical arousal, wakefulness, and sleep, presumably by its regulation of 5-HT2 receptors.
authors.affiliation: Elson S. Floyd College of Medicine, Department of Biomedical Sciences, Washington State University, Spokane, WA.|Sleep and Performance Research Center, Washington State University.|Department of Biological and Medical Psychology, University of Bergen, Norway.
authors.forename: Janne
authors.initials: J
authors.lastname: Grønli
authors.affiliation: Elson S. Floyd College of Medicine, Department of Biomedical Sciences, Washington State University, Spokane, WA.
authors.forename: William C
authors.initials: WC
authors.lastname: Clegern
authors.affiliation: Elson S. Floyd College of Medicine, Department of Biomedical Sciences, Washington State University, Spokane, WA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Schmidt
authors.affiliation: Elson S. Floyd College of Medicine, Department of Biomedical Sciences, Washington State University, Spokane, WA.
authors.forename: Rahmi S
authors.initials: RS
authors.lastname: Nemri
authors.affiliation: Sleep and Performance Research Center, Washington State University.|Mathematics and Computer Science, Whitworth University, Spokane, WA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rempe
authors.affiliation: Department of Basic Medical Sciences and Psychiatry, University of Arizona College of Medicine-Phoenix, Phoenix, AZ.
authors.forename: Amelia L
authors.initials: AL
authors.lastname: Gallitano
authors.affiliation: Elson S. Floyd College of Medicine, Department of Biomedical Sciences, Washington State University, Spokane, WA.|Sleep and Performance Research Center, Washington State University.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Wisor
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D004569:Electroencephalography; D004576:Electromyography; D005260:Female; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics*; D044348:Receptors, Serotonin, 5-HT2 / Q000235:genetics* / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D012890:Sleep / Q000235:genetics* / Q000502:physiology*; D012892:Sleep Deprivation / Q000235:genetics* / Q000503:physiopathology*; D014851:Wakefulness / Q000235:genetics* / Q000502:physiology*
chemical_list: C488358:Erg3 protein, mouse; D015221:Potassium Channels; D044348:Receptors, Serotonin, 5-HT2; D012702:Serotonin Antagonists
keywords: cortical arousal; early growth response; sedation; serotonin