Subcellular localization of GABA_B receptor subunits in rat globus pallidus

The inhibitory amino acid γ-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. © 2004 Wiley-Liss, Inc.