Subcellular Localization of Metabotropic GABABReceptor Subunits GABAB1a/band GABAB2in the Rat Hippocampus

Abstract

Metabotropic GABABreceptors mediate slow inhibitory effects presynaptically and postsynaptically. Using preembedding immunohistochemical methods combined with quantitative analysis of GABABreceptor subunit immunoreactivity, this study provides a detailed description of the cellular and subcellular localization of GABAB1a/band GABAB2in the rat hippocampus. At the light microscopic level, an overlapping distribution of GABAB1a/band GABAB2was revealed in the dendritic layers of the hippocampus. In addition, expression of the GABAB1a/bsubunit was found in somata of CA1 pyramidal cells and of a subset of GABAergic interneurons. At the electron microscopic level, immunoreactivity for both subunits was observed on presynaptic and, more abundantly, on postsynaptic elements. Presynaptically, subunits were mainly detected in the extrasynaptic membrane and occasionally over the presynaptic membrane specialization of putative glutamatergic and, to a lesser extent, GABAergic axon terminals. Postsynaptically, the majority of GABABreceptor subunits were localized to the extrasynaptic plasma membrane of spines and dendritic shafts of principal cells and shafts of interneuron dendrites. Quantitative analysis revealed enrichment of GABAB1a/baround putative glutamatergic synapses on spines and an even distribution on dendritic shafts of pyramidal cells contacted by GABAergic boutons. The association of GABABreceptors with glutamatergic synapses at both presynaptic and postsynaptic sides indicates their intimate involvement in the modulation of glutamatergic neurotransmission. The dominant extrasynaptic localization of GABABreceptor subunits suggests that their activation is dependent on spillover of GABA requiring simultaneous activity of populations of GABAergic cells as it occurs during population oscillations or epileptic seizures.