Differential expression of γ‐aminobutyric acid type B receptor subunit mRNAs in the developing nervous system and receptor coupling to adenylyl cyclase in embryonic neurons

Abstract

γ‐Aminobutyric acid type B receptors (GABABRs) mediate both slow inhibitory synaptic activity in the adult nervous system and motility signals for migrating embryonic cortical cells. Previous papers have described the expression of GABABRs in the adult brain, but the expression and functional significance of these gene products in the embryo are largely unknown. Here we examine GABABR expression from rat embryonic day 10 (E10) to E18 compared with adult and ask whether embryonic cortical neurons contain functional GABABR. GABABR1 transcript levels greatly exceed GABABR2 levels in the developing neural tube at E11, and olfactory bulb and striatum at E17 but equalize in most regions of adult nervous tissue, except for the glomerular and granule cell layers of the main olfactory bulb and the striatum. Consistent with expression differences, the binding affinity of GABA for GABABRs is significantly lower in adult striatum compared with cerebellum. Multiple lines of evidence from in situ hybridization, RNase protection, and real‐time PCR demonstrate that GABABR1a, GABABR1b, GABABR1h (a subunit subtype, lacking a sushi domain, that we have identified in embryonic rat brain), GABABR2, and GABABL transcript levels are not coordinately regulated. Despite the functional requirement for a heterodimer of GABABR subunits, the expression of each subunit mRNA is under independent control during embryonic development, and, by E18, GABABRs are negatively coupled to adenylyl cyclase in neocortical neurons. The presence of embryonic GABABR transcripts and protein and functional receptor coupling indicates potentially important roles for GABABRs in modulation of synaptic transmission in the developing embryonic nervous system.