Localization and pharmacological modulation of GABA-B receptors in the globus pallidus of parkinsonian monkeys

• Type of Material: Article
• Authors: Adriana Galvan, Emory University; Xing Hu, Emory University; Yoland Smith, Emory University; Thomas Wichmann, Emory University
• Language: English
• Date: 2011-06
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.expneurol.2011.03.010
• Title of Journal or Parent Work: Experimental Neurology
• ISSN: 0014-4886
• Volume: 229
• Issue: 2
• Start Page: 429
• End Page: 439
• Grant/Funding Information: This work was supported by NIH grants R01-NS042937 (Y.S.) and RR-00165 (Yerkes National Primate Center).
• Keywords: internal segment of the globus pallidus; in vivo electrophysiology; GABAergic transmission; ultrastructural localization; Parkinson’s disease; External segment of the globus pallidus; nonhuman primate
• Research Categories: Biology, Neuroscience

Abstract

Changes in GABAergic transmission in the external and internal segments of the globus pallidus (GPe and GPi) contribute to the pathophysiology of the basal ganglia network in Parkinson’s disease. Because GABA-B receptors are involved in the modulation of GABAergic transmission in GPe and GPi, it is possible that changes in the functions or localization of these receptors contribute to the changes in GABAergic transmission. To further examine this question, we investigated the anatomical localization of GABA-B receptors and the electrophysiologic effects of microinjections of GABA-B receptor ligands in GPe and GPi of MPTP-treated (parkinsonian) monkeys. We found that the pattern of cellular and ultrastructural localization of the GABA-BR1 subunit of the GABA-B receptor in GPe and GPi was not significantly altered in parkinsonian monkeys. However, the magnitude of reduction in firing rate of GPe and GPi neurons produced by microinjections of the GABA-B receptor agonist baclofen was larger in MPTP-treated animals than in normal monkeys. Injections of the GABA-B receptor antagonist CGP55845A were more effective in reducing the firing rate of GPi neurons in parkinsonian monkeys than in normal animals. In addition, the injections of baclofen in GPe and GPi, or of CGP55845A in GPi lead to a significant increase in the proportion of spikes in rebound bursts in parkinsonian animals, but not in normal monkeys. Thus, despite the lack of changes in the localization of GABA-BR1 subunits in the pallidum, GABA-B receptor-mediated effects are altered in the GPe and GPi of parkinsonian monkeys. These changes in GABA-B receptors function may contribute to bursting activities in the parkinsonian state.