Expression of mRNAs related to the GABAergic and glutamatergic neurotransmitter systems in the human thalamus: normal and schizophrenic

Abstract

Nucleus-specific expression of five gene transcripts related to the inhibitory, gamma-aminobutyric acid (GABA), neurotransmitter system (GABA_A receptor subunits α1, α5, β2, γ2, and 67 kDa glutamic acid decarboxylase (GAD₆₇)), and of seven transcripts related to the excitatory, glutamatergic, system (GluR2, 4–6, NR1 and NR2A, and α-type II calcium/calmodulin-dependent protein kinase (CAMKII-α)), were examined by quantitative in situ hybridization histochemistry in the thalami of brains from normal controls and from patients suffering from schizophrenia. Although there is evidence for cell loss and functional hypoactivity in the thalamus in schizophrenia, it was striking that quantitative levels and expression patterns of the transcripts studied showed only minor differences between schizophrenics and matched controls. Expression patterns of the transcripts had many similarities to the patterns seen in the thalamus of non-human primates. Abundant GABA_A-α1, GABA_A-β2, and GABA_A-γ2 subunit mRNAs levels were found in most nuclei. Expression levels of the NMDA receptor subunit, NR1, were higher than those seen for NR2A, AMPA (GluR2 and 4) or kainate (GluR5 and 6) receptor subunit mRNAs. Expression of NR2A mRNA was extremely low. CAMKII-α expression was restricted to glutamatergic neurons. Unlike in monkeys, GluR2 subunit mRNA expression was higher than GluR4 expression. These expression patterns form the beginning of a comprehensive database of patterns of gene expression at high resolution in the human forebrain in health and disease.