Subcellular localization of GABAB receptor subunits in rat globus pallidus.

Abstract

The inhibitory amino acid gamma-aminobutyric acid (GABA) is the major neurotransmitter in the globus pallidus. Although electrophysiological studies have indicated that functional GABA(B) receptors exist in rat globus pallidus, the subcellular localization of GABA(B) receptor subunits and their spatial relationship to glutamatergic and GABAergic synapses are unknown. Here, we use pre-embedding immunogold labeling to study the subcellular localization of GABA(B) receptor subunits, GABA(B1) and GABA(B2), in globus pallidus neurons and identified populations of afferent terminals. Immunolabeling for GABA(B1) and GABA(B2) was observed throughout the globus pallidus, with GABA(B1) more strongly expressed in perikarya and GABA(B2) mainly expressed in the neuropil. Electron microscopic analysis revealed that the majority of GABA(B1) labeling was localized within the cytoplasm, whereas most of GABA(B2) labeling was associated with the plasma membrane. At the subcellular level, both the GABA(B1) and GABA(B2) immunogold labeling was localized at pre- and postsynaptic sites. At asymmetric, putative excitatory, synapses, GABA(B1) and GABA(B2) immunogold labeling was found at perisynaptic sites of both pre- and postsynaptic specializations. Double immunolabeling, using the vesicular glutamate transporter 2 (VGLUT2), revealed the glutamatergic nature of most immunogold-labeled asymmetric synapses. At symmetric, putative GABAergic, synapses, including those formed by anterogradely labeled striatopallidal terminals, GABA(B1) and GABA(B2) immunogold labeling was found in the main body of both pre- and postsynaptic specializations. These results demonstrate the existence of presynaptic GABA(B) auto- and heteroreceptors and postsynaptic GABA(B) receptors, which may be involved in modulating synaptic transmission in the globus pallidus.