Synaptic localization of GABA(A) receptor subunits in the striatum of the rat

The inhibitory amino acid gamma-aminobutyric acid (GABA) is widely distribu ted in the basal ganglia. It plays a critical role in the functioning of th e striatum as it is the transmitter of projection neurons and sub-populatio ns 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 ex amined the sub-cellular localization of subunits of the GABA(A) receptor in the striatum of the rat. Sections of freeze-substituted, Lowicryl-embedded striatum were immunolabelled by the post-embedding immunogold technique wi th antibodies specific for subunits of the GABA(A) receptor. Immunolabellin g for alpha 1, beta 2/3, and gamma 2 GABA(A) receptor subunits was primaril y located at symmetrical synapses on perikarya, dendrites, and spines. Quan titative analysis of the distribution of immunolabelling for the beta 2/3 s ubunits revealed that the majority of membrane associated immunogold partic les were at synapses and that, on average for the whole population, they we re evenly distributed across the synapse. Double labelling for the beta 2/3 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, wherea s the other (40.7%) had low or undetectable levels of GABA. Furthermore, th e post-synaptic neurons were characterised on neurochemical and morphologic al grounds as both medium spiny neurons and GABA interneurons. Triple immun olabelling revealed the co-localization of alpha 1, beta 2/3, and gamma 2 s ubunits at some symmetrical axodendritic synapse. It is concluded that fast GABA(A)-mediated transmission occurs primarily at symmetrical synapses wit hin the striatum, that the populations of boutons giving rise to receptor-p ositive synapses are heterogeneous, and that previously reported co-existen ce of different subunits of the GABA(A) receptor at the cellular level also occurs at the level of individual synapses. J. Comp. Neurol. 416:158-172, 2000. (C) 2000 Wiley-Liss, Inc.