title: Kv2.2: a novel molecular target to study the role of basal forebrain GABAergic neurons in the sleep-wake cycle.
abstract: OBJECTIVE
  The basal forebrain (BF) has been implicated as an important brain region that regulates the sleep-wake cycle of animals. Gamma-aminobutyric acidergic (GABAergic) neurons are the most predominant neuronal population within this region. However, due to the lack of specific molecular tools, the roles of the BF GABAergic neurons have not been fully elucidated. Previously, we have found high expression levels of the Kv2.2 voltage-gated potassium channel on approximately 60% of GABAergic neurons in the magnocellular preoptic area and horizontal limb of the diagonal band of Broca of the BF and therefore proposed it as a potential molecular target to study this neuronal population. In this study, we sought to determine the functional roles of the Kv2.2-expressing neurons in the regulation of the sleep-wake cycle.
  
  
  METHODS
  Sleep analysis between two genotypes and within each genotype before and after sleep deprivation.
  
  
  METHODS
  Animal sleep research laboratory.
  
  
  METHODS
  Adult mice. Wild-type and Kv2.2 knockout mice with C57/BL6 background.
  
  
  METHODS
  EEG/EMG recordings from the basal state and after sleep-deprivation which was induced by mild agitation for 6 h.
  
  
  RESULTS
  Immunostaining of a marker of neuronal activity indicates that these Kv2.2-expressing neurons appear to be preferentially active during the wake state. Therefore, we tested whether Kv2.2-expressing neurons in the BF are involved in arousal using Kv2.2-deficient mice. BF GABAergic neurons exhibited augmented expression of c-Fos. These knockout mice exhibited longer consolidated wake bouts than wild-type littermates, and that phenotype was further exacerbated by sleep deprivation. Moreover, in-depth analyses of their cortical electroencephalogram revealed a significant decrease in the delta-frequency activity during the nonrapid eye movement sleep state.
  
  
  CONCLUSIONS
  These results revealed the significance of Kv2.2-expressing neurons in the regulation of the sleep-wake cycle.
authors.affiliation: Department of Neural and Pain Sciences ; Program in Neurosciences ; Department of Developmental Biology, Washington University, St. Louis, MO.
authors.forename: Tracey O
authors.initials: TO
authors.lastname: Hermanstyne
authors.forename: Kalpana
authors.initials: K
authors.lastname: Subedi
authors.forename: Wei Wei
authors.initials: WW
authors.lastname: Le
authors.forename: Gloria E
authors.initials: GE
authors.lastname: Hoffman
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Meredith
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Mong
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Misonou
mesh_terms: D000818:Animals; D004569:Electroencephalography; D004576:Electromyography; D059330:GABAergic Neurons / Q000502:physiology*; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D010320:Parvalbumins / Q000502:physiology; D016548:Prosencephalon / Q000166:cytology / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology; D051669:Shab Potassium Channels / Q000235:genetics / Q000502:physiology*; D012890:Sleep / Q000235:genetics / Q000502:physiology*; D012892:Sleep Deprivation / Q000503:physiopathology; D014851:Wakefulness / Q000235:genetics / Q000502:physiology*
chemical_list: D010320:Parvalbumins; D016760:Proto-Oncogene Proteins c-fos; D051669:Shab Potassium Channels
keywords: Channel; GABA; basal forebrain; cortex