Selective expression of KCNS3 potassium channel α-subunit in parvalbumin-containing GABA neurons in the human prefrontal cortex

Georgiev, D and González-Burgos, G and Kikuchi, M and Minabe, Y and Lewis, DA and Hashimoto, T (2012) Selective expression of KCNS3 potassium channel α-subunit in parvalbumin-containing GABA neurons in the human prefrontal cortex. PLoS ONE, 7 (8).

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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 35S- 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. © 2012 Georgiev et al.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Georgiev, D González-Burgos, G Kikuchi, M Minabe, Y Lewis, DA tnplewis@pitt.edu TNPLEWIS Hashimoto, T
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Yoshikawa, Takeo UNSPECIFIED UNSPECIFIED UNSPECIFIED
Date:	24 August 2012
Date Type:	Publication
Journal or Publication Title:	PLoS ONE
Volume:	7
Number:	8
DOI or Unique Handle:	10.1371/journal.pone.0043904
Schools and Programs:	Dietrich School of Arts and Sciences > Neuroscience School of Medicine > Psychiatry
Refereed:	Yes
Other ID:	NLM PMC3427167
PubMed Central ID:	PMC3427167
PubMed ID:	22937123
Date Deposited:	18 Oct 2012 21:04
Last Modified:	22 Jun 2021 13:55
URI:	http://d-scholarship.pitt.edu/id/eprint/15892

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