title: Cacna1c (Cav1.2) Modulates Electroencephalographic Rhythm and Rapid Eye Movement Sleep Recovery.
abstract: OBJECTIVE
  The CACNA1C gene encodes the alpha 1C (α1C) subunit of the Cav1.2 voltage-dependent L-type calcium channel (LTCC). Some of the other voltage-dependent calcium channels, e.g., P-/Q-type, Cav2.1; N-type, Cav2.2; E-/R-type, Cav2.3; and T-type, Cav3.3 have been implicated in sleep modulation. However, the contribution of LTCCs to sleep remains largely unknown. Based on recent genome-wide association studies, CACNA1C emerged as one of potential candidate genes associated with both sleep and psychiatric disorders. Indeed, most patients with mental illnesses have sleep problems and vice versa.
  
  
  METHODS
  To investigate an impact of Cav1.2 on sleep-wake behavior and electroencephalogram (EEG) activity, polysomnography was performed in heterozygous Cacna1c (HET) knockout mice and their wild-type (WT) littermates under baseline and challenging conditions (acute sleep deprivation and restraint stress).
  
  
  RESULTS
  HET mice displayed significantly lower EEG spectral power than WT mice across high frequency ranges (beta to gamma) during wake and rapid eye movement (REM) sleep. Although HET mice spent slightly more time asleep in the dark period, daily amounts of sleep did not differ between the two genotypes. However, recovery sleep after exposure to both types of challenging stress conditions differed markedly; HET mice exhibited reduced REM sleep recovery responses compared to WT mice.
  
  
  CONCLUSIONS
  These results suggest the involvement of Cacna1c (Cav1.2) in fast electroencephalogram oscillations and REM sleep regulatory processes. Lower spectral gamma activity, slightly increased sleep demands, and altered REM sleep responses found in heterozygous Cacna1c knockout mice may rather resemble a sleep phenotype observed in schizophrenia patients.
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Deependra
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.|Institute of Developmental Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Dedic
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Flachskamm
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Voulé
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Deussing
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kimura
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D004569:Electroencephalography; D065818:Gamma Rhythm / Q000502:physiology*; D006579:Heterozygote; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017286:Polysomnography; D012149:Restraint, Physical; D012892:Sleep Deprivation / Q000503:physiopathology; D012895:Sleep, REM / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology
chemical_list: C514350:CACNA1C protein, mouse; D020746:Calcium Channels, L-Type
keywords: Cacna1c; Cav1.2; EEG spectral power; L-type voltage-dependent calcium channel; schizophrenia; sleep
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