An in situ hybridization study of the distribution of the GABA(B2) proteinmRNA in the rat CNS

gamma-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in t he mammalian central nervous system. GABA exerts its actions through two cl asses of receptors: GABA(A), multimeric ligand-gated Cl- ion channels (a cl ass which has been proposed to include the homomeric variant previously cal led GABA(C), to be designated GABA(A0r)); and GABA(B), G-protein coupled re ceptors which regulate Ca2+ and K+ channels. Currently, within the GABA(B) receptor family two proteins have been identified through molecular cloning techniques and designated GABA(B1) and GABA(B2). Two N-terminal variants o f GABA(B1) were isolated and designated GABA(B1a) and GABA(B1b). The distri bution of neurons in the rat CNS expressing the mRNA for the GABA(B1) isofo rms have been previously described by in situ hybridization histochemistry. The recent isolation and identification of the GABA(B2) protein by homolog y cloning has enabled the use of radiolabeled oligonucleotides to detect th e distribution of the expression of GABA(B2) mRNA in the rat CNS. The expre ssion of GABA(B2) mRNA was observed to be primarily related to neuronal pro files. The highest levels of GABA,, mRNA expression were detected in the pi riform cortex, hippocampus, and medial habenula. GABA(B2) mRNA was abundant in all layers of the cerebral cortex, the thalamus and in cerebellar Purki nje cells. Moderate expression was observed in several hypothalamic and bra instem nuclei. In contrast to the distribution of GABA(B1) mRNA, only a wea k hybridization signal for GABA(B2) was detected over cells of the basal ga nglia, including the caudate-putamen, nucleus accumbens, olfactory tubercle and throughout most of the hypothalamus. Moderate-to-heavy GABA(B2) mRNA e xpression was also seen over dorsal root and trigeminal ganglion cells. In general, the pattern of GABA(B2) mRNA expression in the rat brain overlaps considerably with the distributions described for both GABA(B1) mRNAs, and is concordant with the distribution described for GABA(B) receptor binding sites. However, differences between GABA(B2) expression levels and GABA(B) binding sites were observed in the basal ganglia. (C) 1999 Elsevier Science B.V. All rights reserved.