An in situ hybridization study of the distribution of the GABA sub(B2) protein mRNA in the rat CNS

gamma -Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian central nervous system. GABA exerts its actions through two classes of receptors: GABA sub(A), multimeric ligand-gated Cl super(-) ion channels (a class which has been proposed to include the homomeric variant previously called GABA sub(C), to be designated GABA sub(A0r)); and GABA sub(B), G-protein coupled receptors which regulate Ca super(2+) and K super(+) channels. Currently, within the GABA sub(B) receptor family two proteins have been identified through molecular cloning techniques and designated GABA sub(B1) and GABA sub(B2). Two N-terminal variants of GABA sub(B1) were isolated and designated GABA sub(B1a) and GABA sub(B1b). The distribution of neurons in the rat CNS expressing the mRNA for the GABA sub(B1) isoforms have been previously described by in situ hybridization histochemistry. The recent isolation and identification of the GABA sub(B2) protein by homology cloning has enabled the use of radiolabeled oligonucleotides to detect the distribution of the expression of GABA sub(B2) mRNA in the rat CNS. The expression of GABA sub(B2) mRNA was observed to be primarily related to neuronal profiles. The highest levels of GABA sub(B2) mRNA expression were detected in the piriform cortex, hippocampus, and medial habenula. GABA sub(B2) mRNA was abundant in all layers of the cerebral cortex, the thalamus and in cerebellar Purkinje cells. Moderate expression was observed in several hypothalamic and brainstem nuclei. In contrast to the distribution of GABA sub(B1) mRNA, only a weak hybridization signal for GABA sub(B2) was detected over cells of the basal ganglia, including the caudate-putamen, nucleus accumbens, olfactory tubercle and throughout most of the hypothalamus. Moderate-to-heavy GABA sub(B2) mRNA expression was also seen over dorsal root and trigeminal ganglion cells. In general, the pattern of GABA sub(B2) mRNA expression in the rat brain overlaps considerably with the distributions described for both GABA sub(B1) mRNAs, and is concordant with the distribution described for GABA sub(B) receptor binding sites. However, differences between GABA sub(B2) expression levels and GABA sub(B) binding sites were observed in the basal ganglia.