Cerebral Cortex 1995; 5:550-560
© Oxford University Press 1995
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GABAA Receptor Subunit Gene Expression in Human Prefrontal Cortex: Comparison of Schizophrenics and Controls
1Department of Anatomy and Neurobiology, University of California Irvine, California 92717, 2Department of Psychiatry and Human Behavior, University of California Irvine, California 92717
The prefrontal cortex of schizophrenics is hypoactive and displays changes related to inhibitory, GABAergic neurons, and GABAergic synapses. These changes include decreased levels of glutamic acid decarboxylase (GAD), the enzyme for GABA synthesis, upregulation of muscimol binding, and downregulation of benzodiazepine binding to GABAA receptors. Studies in the visual cortex of nonhuman primates have demonstrated that gene expression for GAD and for several GABAA receptor subunit polypeptides is under control of neuronal activity, raising the possibility that similar mechanisms in the hypoactive prefrontal cortex of schizophrenics may explain the abnormalities in GAD and in GABAA receptor regulation.
In the present study, which is the first of its type on human cerebral cortex, levels of mRNAs for six GABAA receptor subunits (
1, 2, 5, ß1, ß2, 
2) and their laminar expression patterns were analyzed in the prefrontal cortex of schizophrenics and matched controls, using in situ hybridization histochemistry and densitomotry.
Three types of laminar expression pattern were observed: mRNAs for the 1, ß2 and 2 subunits, which are the predominant receptor subunits expressed in the mature cortex, were expressed at comparatively high levels by cells of all six cortical layers, but most intensely by cells in lower layer III and layer IV. mRNAs for the 2, 5, and ß1 subunits were expressed at lower levels; 2 and ß1 were expressed predominantly by cells in layers II, III, and IV; 5 was expressed predominantly in layers IV, V, and Vl. There were no significant changes in overall mRNA levels for any of the receptor subunits in the prefrontal cortex of schizophrenics, and the laminar expression pattern of all six receptor subunit mRNAs did not differ between schizophrenics and controls.
Because gene expression for GABAA receptor subunits is not consistently altered in the prefrontal cortex of schizophrenics, the previously reported upregulation of muscimol binding sites and downregulation of benzodiazepine binding sites in the prefrontal and adjacent cingulate cortex of schizophrenics are possibly due to posttranscriptional modifications of mRNAs and their translated polypeptides.
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