Distribution of metabotropic GABA receptor subunits GABAB1a/b and GABAB2 in the rat hippocampus during prenatal and postnatal development

Metabotropic γ-aminobutyric acid receptors (GABAB) play modulatory roles in central synaptic transmission and are involved in controlling neuronal migration during development. We used immunohistochemical methods to elucidate the expression pattern as well as the cellular and the precise subcellular localization of the GABAB1a/b and GABAB2 subunits in the rat hippocampus during prenatal and postnatal development. At the light microscopic level, both GABABB1a/b and GABAB2 were expressed in the hippocampal primordium from embryonic day E14. During postnatal development, immunoreactivity for GABAB1a/b and GABAB2 was distributed mainly in pyramidal cells, with discrete GABABB1a/b-immunopositive cell bodies of interneurons present throughout the hippocampus. Using double immunofluorescence, we demonstrated that during the second week of postnatal development, GABAB1a/b but not GABAB2 was expressed in glial cells throughout the hippocampal formation. At the electron microscopic level, GABAB1a/b and GABAB2 showed a similar distribution pattern during postnatal development. Thus, at all ages the two receptor subunits were located postsynaptically in dendritic spines and shafts at extrasynaptic and perisynaptic sites in both pyramidal and nonpyramidal cells. We further demonstrated that the two subunits were localized presynaptically along the extrasynaptic plasma membrane of axon terminals and along the presynaptic active zone in both asymmetrical and, to a lesser extent, symmetrical synapses. These results suggest that GABAB receptors are widely expressed in the hippocampus throughout development and that GABABB1a/b and GABAB2 form both pre- and postsynaptic receptors.