Synaptic localization of GABAA receptor subunits in the striatum of the rat

Abstract

The inhibitory amino acid γ-aminobutyric acid (GABA) is widely distributed in the basal ganglia. It plays a critical role in the functioning of the striatum as it is the transmitter of projection neurons and sub-populations of interneurons, as well as afferents from the globus pallidus. Some of the factors controlling GABA transmission are the type(s) of GABA receptor expressed at the site of transmission, their subunit composition, and their location in relation to GABA release sites. To address these issues, we examined the sub-cellular localization of subunits of the GABAA receptor in the striatum of the rat. Sections of freeze-substituted, Lowicryl-embedded striatum were immunolabelled by the post-embedding immunogold technique with antibodies specific for subunits of the GABAA receptor. Immunolabelling for α1, β2/3, and γ2 GABAA receptor subunits was primarily located at symmetrical synapses on perikarya, dendrites, and spines. Quantitative analysis of the distribution of immunolabelling for the β2/3 subunits revealed that the majority of membrane associated immunogold particles were at synapses and that, on average for the whole population, they were evenly distributed across the synapse. Double labelling for the β2/3 subunits and for GABA itself revealed that receptor-positive synapses were formed by at least two populations of terminals. One population (59.3%) of terminals forming receptor-positive synapses was positive for GABA, whereas the other (40.7%) had low or undetectable levels of GABA. Furthermore, the post-synaptic neurons were characterised on neurochemical and morphological grounds as both medium spiny neurons and GABA interneurons. Triple immunolabelling revealed the co-localization of α1, β2/3, and γ2 subunits at some symmetrical axodendritic synapse. It is concluded that fast GABAA-mediated transmission occurs primarily at symmetrical synapses within the striatum, that the populations of boutons giving rise to receptor-positive synapses are heterogeneous, and that previously reported co-existence of different subunits of the GABAA receptor at the cellular level also occurs at the level of individual synapses. J. Comp. Neurol. 416:158–172, 2000. © 2000 Wiley-Liss, Inc.