Spatial distribution of GABA(B)R1 receptor mRNA and binding sites in the rat brain

A gamma-aminobutyric acid (GABA)(B) receptor (named GABA(B)R1) has been rec ently cloned in the rat and human brain and two variants generated by alter native RNA splicing were identified. In the present study, we addressed the question as to whether these variants contribute to the diversity of GABAB receptor-mediated physiological responses and constitute real receptor sub types with distinct functions. To this aim, we have mapped the GABA(B)R1 (R 1a) and GABA(B)R1b (R1b) transcript distribution in the rat brain using in situ hybridization. We have compared the mRNA distribution with the distrib ution of [H-3] CGP54626-labeled binding GABA(B)R1 receptor sites as assesse d in adjacent cryosections by quantitative autoradiography. We found that G ABA(B) receptor transcripts and binding sites are expressed in the brain in almost all neuronal cell populations. Expression in glial cells, if any, i s marginal. We observed a good parallelism between GABA(B)R1 mRNA transcrip ts and binding sites in broad neuroanatomical entities with highest densiti es in hippocampus, thalamic nuclei, and cerebellum. By contrast, R1a and Ri b transcripts exhibit marked differences in their regional and cellular dis tribution pattern. A typical example is the cerebellum with an almost exclu sive expression of Rib in the Purkinje cells and of R1a in the granule, ste llate, and basket cells. Data pointing at a pre- versus postsynaptic locali zation for R1a and Rib, respectively, at some neuronal sites are presented. (C) 1999 Wiley-Liss, Inc.