Differential subcellular and subsynaptic distribution of GABA(A) and GABA(B) receptors in the monkey subthalamic nucleus

Abstract

The activation of GABA receptor subtype A (GABA(A)) and GABA receptor subtype B (GABA(B)) receptors mediates differential effects on GABAergic and non-GABAergic transmission in the basal ganglia. To further characterize the anatomical substrate that underlies these functions, we used immunogold labeling to compare the subcellular and subsynaptic localization of GABA(A) and GABA(B) receptors in the subthalamic nucleus (STN). Our findings demonstrate major differences and some similarities in the distribution of GABA(A) and GABA(B) receptors in the monkey STN. The immunoreactivity for GABA(A) receptor alpha1 subunits is mostly bound to the plasma membrane, whereas GABA(B) R1 subunit alpha1 immunoreactivity is largely expressed intracellularly. Plasma membrane-bound GABA(A) alpha1 subunit aggregate in the main body of putative GABAergic synapses, while GABA(B) R1 receptors are found at the edges of putative glutamatergic or GABAergic synapses. A large pool of plasma membrane-bound GABA(A) and GABA(B) receptors is extrasynaptic. In conclusion, these findings demonstrate a significant degree of heterogeneity between the distributions of the two major GABA receptor subtypes in the monkey STN. Their pattern of synaptic localization puts forward interesting questions regarding their mechanisms of activation and functions at GABAergic and non-GABAergic synapses.