title: Lower gene expression for KCNS3 potassium channel subunit in parvalbumin-containing neurons in the prefrontal cortex in schizophrenia.
abstract: OBJECTIVE
  In schizophrenia, alterations in markers of cortical GABA neurotransmission are prominent in parvalbumin-containing neurons. Parvalbumin neurons selectively express KCNS3, the gene encoding the Kv9.3 potassium channel α-subunit. Kv9.3 subunits are present in voltage-gated potassium channels that contribute to the precise detection of coincident excitatory synaptic inputs to parvalbumin neurons. This distinctive feature of parvalbumin neurons appears important for the synchronization of cortical neural networks in γ-oscillations. Because impaired prefrontal cortical γ-oscillations are thought to underlie the cognitive impairments in schizophrenia, the authors investigated whether KCNS3 mRNA levels are altered in the prefrontal cortex of schizophrenia subjects.
  
  
  METHODS
  KCNS3 mRNA expression was evaluated by in situ hybridization in 22 matched pairs of schizophrenia and comparison subjects and by microarray analyses of pooled samples of individually dissected neurons that were labeled with Vicia villosa agglutinin (VVA), a parvalbumin neuron-selective marker, in a separate cohort of 14 pairs. Effects of chronic antipsychotic treatments on KCNS3 expression were tested in the prefrontal cortex of antipsychotic-exposed monkeys.
  
  
  RESULTS
  By in situ hybridization, KCNS3 mRNA levels were 23% lower in schizophrenia subjects. At the cellular level, both KCNS3 mRNA-expressing neuron density and KCNS3 mRNA level per neuron were significantly lower. By microarray, KCNS3 mRNA levels were lower by 40% in VVA-labeled neurons from schizophrenia subjects. KCNS3 mRNA levels were not altered in antipsychotic-exposed monkeys.
  
  
  CONCLUSIONS
  These findings reveal lower KCNS3 expression in prefrontal cortical parvalbumin neurons in schizophrenia, providing a molecular basis for compromised detection of coincident synaptic inputs to parvalbumin neurons that could contribute to altered γ-oscillations and impaired cognition in schizophrenia.
authors.forename: Danko
authors.initials: D
authors.lastname: Georgiev
authors.forename: Dominique
authors.initials: D
authors.lastname: Arion
authors.forename: John F
authors.initials: JF
authors.lastname: Enwright
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Minabe
authors.forename: John P
authors.initials: JP
authors.lastname: Corradi
authors.forename: David A
authors.initials: DA
authors.lastname: Lewis
authors.forename: Takanori
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; C489356:KCNS3 protein, human; D010320:Parvalbumins; D024642:Potassium Channels, Voltage-Gated