title: Selective expression of KCNS3 potassium channel α-subunit in parvalbumin-containing GABA neurons in the human prefrontal cortex.
abstract: The cognitive deficits of schizophrenia appear to be associated with altered cortical GABA neurotransmission in the subsets of inhibitory neurons that express either parvalbumin (PV) or somatostatin (SST). Identification of molecular mechanisms that operate selectively in these neurons is essential for developing targeted therapeutic strategies that do not influence other cell types. Consequently, we sought to identify, in the human cortex, gene products that are expressed selectively by PV and/or SST neurons, and that might contribute to their distinctive functional properties. Based on previously reported expression patterns in the cortex of mice and humans, we selected four genes: KCNS3, LHX6, KCNAB1, and PPP1R2, encoding K(+) channel Kv9.3 modulatory α-subunit, LIM homeobox protein 6, K(+) channel Kvβ1 subunit, and protein phosphatase 1 regulatory subunit 2, respectively, and examined their colocalization with PV or SST mRNAs in the human prefrontal cortex using dual-label in situ hybridization with (35)S- and digoxigenin-labeled antisense riboprobes. KCNS3 mRNA was detected in almost all PV neurons, but not in SST neurons, and PV mRNA was detected in >90% of KCNS3 mRNA-expressing neurons. LHX6 mRNA was detected in almost all PV and >90% of SST neurons, while among all LHX6 mRNA-expressing neurons 50% expressed PV mRNA and >44% expressed SST mRNA. KCNAB1 and PPP1R2 mRNAs were detected in much larger populations of cortical neurons than PV or SST neurons. These findings indicate that KCNS3 is a selective marker of PV neurons, whereas LHX6 is expressed by both PV and SST neurons. KCNS3 and LHX6 might be useful for characterizing cell-type specific molecular alterations of cortical GABA neurotransmission and for the development of novel treatments targeting PV and/or SST neurons in schizophrenia.
authors.affiliation: Department of Psychiatry and Neurobiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
authors.forename: Danko
authors.initials: D
authors.lastname: Georgiev
authors.forename: Guillermo
authors.initials: G
authors.lastname: González-Burgos
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Minabe
authors.forename: David A
authors.initials: DA
authors.lastname: Lewis
authors.forename: Takanori
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000235:genetics / Q000378:metabolism*; D000097847:Protein Phosphatase Inhibitory Proteins
chemical_list: D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D024642:Potassium Channels, Voltage-Gated; D011506:Proteins; D014157:Transcription Factors; D005680:gamma-Aminobutyric Acid; C489356:KCNS3 protein, human; C121947:LHX6 protein, human; C024833:protein phosphatase inhibitor-2; D000097847:Protein Phosphatase Inhibitory Proteins