Spatial distribution of GABABR1 receptor mRNA and binding sites in the rat brain

Abstract

A γ-aminobutyric acid (GABA)B receptor (named GABABR1) has been recently cloned in the rat and human brain and two variants generated by alternative 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 subtypes with distinct functions. To this aim, we have mapped the GABABR1 (R1a) and GABABR1b (R1b) transcript distribution in the rat brain using in situ hybridization. We have compared the mRNA distribution with the distribution of [3H]CGP54626-labeled binding GABABR1 receptor sites as assessed in adjacent cryosections by quantitative autoradiography. We found that GABAB receptor transcripts and binding sites are expressed in the brain in almost all neuronal cell populations. Expression in glial cells, if any, is marginal. We observed a good parallelism between GABABR1 mRNA transcripts and binding sites in broad neuroanatomical entities with highest densities in hippocampus, thalamic nuclei, and cerebellum. By contrast, R1a and R1b transcripts exhibit marked differences in their regional and cellular distribution pattern. A typical example is the cerebellum with an almost exclusive expression of R1b in the Purkinje cells and of R1a in the granule, stellate, and basket cells. Data pointing at a pre- versus postsynaptic localization for R1a and R1b, respectively, at some neuronal sites are presented. J. Comp. Neurol. 412:1–16, 1999. © 1999 Wiley-Liss, Inc.