Localization and Pharmacological Modulation of GABA-B Receptors in the Globus Pallidus of Parkinsonian Monkeys

Overview

Journal Exp Neurol

Specialty Neurology

Date 2011 Mar 23

PMID 21419765

Citations 16

Authors

Adriana Galvan

Xing Hu

Yoland Smith

Thomas Wichmann

Affiliations

Soon will be listed here.

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 receptor function may contribute to bursting activities in the parkinsonian state.

Citing Articles

Structural Plasticity of GABAergic Pallidothalamic Terminals in MPTP-Treated Parkinsonian Monkeys: A 3D Electron Microscopic Analysis.

Masilamoni G, Kelly H, Swain A, Pare J, Villalba R, Smith Y eNeuro. 2024; 11(3).

PMID: 38514185 PMC: 10957232. DOI: 10.1523/ENEURO.0241-23.2024.

Pallidal GABA B receptors: involvement in cortex beta dynamics and thalamic reticular nucleus activity.

Villalobos N, Magdaleno-Madrigal V J Physiol Sci. 2023; 73(1):14.

PMID: 37328793 PMC: 10717573. DOI: 10.1186/s12576-023-00870-8.

Integrative opioid-GABAergic neuronal mechanisms regulating dopamine efflux in the nucleus accumbens of freely moving animals.

Saigusa T, Aono Y, Waddington J Pharmacol Rep. 2021; 73(4):971-983.

PMID: 33743175 DOI: 10.1007/s43440-021-00249-9.

Ultrapotent chemogenetics for research and potential clinical applications.

Magnus C, Lee P, Bonaventura J, Zemla R, Gomez J, Ramirez M Science. 2019; 364(6436).

PMID: 30872534 PMC: 7252514. DOI: 10.1126/science.aav5282.

Sub-synaptic localization of Ca3.1 T-type calcium channels in the thalamus of normal and parkinsonian monkeys.

Chen E, Pare J, Wichmann T, Smith Y Brain Struct Funct. 2016; 222(2):735-748.

PMID: 27255751 PMC: 5135628. DOI: 10.1007/s00429-016-1242-9.

References

Kliem M, Wichmann T . A method to record changes in local neuronal discharge in response to infusion of small drug quantities in awake monkeys. J Neurosci Methods. 2004; 138(1-2):45-9. DOI: 10.1016/j.jneumeth.2004.03.015. View

Hutchison W, Lozano A, Davis K, Saint-Cyr J, Lang A, Dostrovsky J . Differential neuronal activity in segments of globus pallidus in Parkinson's disease patients. Neuroreport. 1994; 5(12):1533-7. DOI: 10.1097/00001756-199407000-00031. View

Galvan A, Kuwajima M, Smith Y . Glutamate and GABA receptors and transporters in the basal ganglia: what does their subsynaptic localization reveal about their function?. Neuroscience. 2006; 143(2):351-75. PMC: 2039707. DOI: 10.1016/j.neuroscience.2006.09.019. View

Nielsen J, Conway B, Halliday D, Perreault M, Hultborn H . Organization of common synaptic drive to motoneurones during fictive locomotion in the spinal cat. J Physiol. 2005; 569(Pt 1):291-304. PMC: 1464221. DOI: 10.1113/jphysiol.2005.091744. View

Stanford I . Independent neuronal oscillators of the rat globus pallidus. J Neurophysiol. 2003; 89(3):1713-7. DOI: 10.1152/jn.00864.2002. View

Wichmann T, Kliem M, DeLong M . Antiparkinsonian and behavioral effects of inactivation of the substantia nigra pars reticulata in hemiparkinsonian primates. Exp Neurol. 2001; 167(2):410-24. DOI: 10.1006/exnr.2000.7572. View

Scanziani M . GABA spillover activates postsynaptic GABA(B) receptors to control rhythmic hippocampal activity. Neuron. 2000; 25(3):673-81. DOI: 10.1016/s0896-6273(00)81069-7. View

Lacey C, Boyes J, Gerlach O, Chen L, Magill P, Bolam J . GABA(B) receptors at glutamatergic synapses in the rat striatum. Neuroscience. 2005; 136(4):1083-95. DOI: 10.1016/j.neuroscience.2005.07.013. View

Soares J, Kliem M, Betarbet R, Greenamyre J, Yamamoto B, Wichmann T . Role of external pallidal segment in primate parkinsonism: comparison of the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism and lesions of the external pallidal segment. J Neurosci. 2004; 24(29):6417-26. PMC: 6729864. DOI: 10.1523/JNEUROSCI.0836-04.2004. View

10.

Charara A, Heilman T, Levey A, Smith Y . Pre- and postsynaptic localization of GABA(B) receptors in the basal ganglia in monkeys. Neuroscience. 2000; 95(1):127-40. DOI: 10.1016/s0306-4522(99)00409-1. View

11.

Pin J, Comps-Agrar L, Maurel D, Monnier C, Rives M, Trinquet E . G-protein-coupled receptor oligomers: two or more for what? Lessons from mGlu and GABAB receptors. J Physiol. 2009; 587(Pt 22):5337-44. PMC: 2793868. DOI: 10.1113/jphysiol.2009.179978. View

12.

De Groote C, Wullner U, Lochmann P, Luiten P, Klockgether T . Functional characterization and expression of thalamic GABA(B) receptors in a rodent model of Parkinson's disease. Neuropharmacology. 1999; 38(11):1683-9. DOI: 10.1016/s0028-3908(99)00125-2. View

13.

Lee S, Yoon B, Berglund K, Oh S, Park H, Shin H . Channel-mediated tonic GABA release from glia. Science. 2010; 330(6005):790-6. DOI: 10.1126/science.1184334. View

14.

Galvan A, Charara A, Pare J, Levey A, Smith Y . Differential subcellular and subsynaptic distribution of GABA(A) and GABA(B) receptors in the monkey subthalamic nucleus. Neuroscience. 2004; 127(3):709-21. DOI: 10.1016/j.neuroscience.2004.05.014. View

15.

Nakanishi H, Kita H, Kitai S . Intracellular study of rat entopeduncular nucleus neurons in an in vitro slice preparation: electrical membrane properties. Brain Res. 1990; 527(1):81-8. DOI: 10.1016/0006-8993(90)91063-m. View

16.

Bevan M, Hallworth N, Baufreton J . GABAergic control of the subthalamic nucleus. Prog Brain Res. 2007; 160:173-88. DOI: 10.1016/S0079-6123(06)60010-1. View

17.

Kita H . Globus pallidus external segment. Prog Brain Res. 2007; 160:111-33. DOI: 10.1016/S0079-6123(06)60007-1. View

18.

Chen L, Chan S, Yung W . Rotational behavior and electrophysiological effects induced by GABA(B) receptor activation in rat globus pallidus. Neuroscience. 2002; 114(2):417-25. DOI: 10.1016/s0306-4522(02)00299-3. View

19.

Rudolph U, Mohler H . Analysis of GABAA receptor function and dissection of the pharmacology of benzodiazepines and general anesthetics through mouse genetics. Annu Rev Pharmacol Toxicol. 2004; 44:475-98. DOI: 10.1146/annurev.pharmtox.44.101802.121429. View

20.

Charara A, Pare J, Levey A, Smith Y . Synaptic and extrasynaptic GABA-A and GABA-B receptors in the globus pallidus: an electron microscopic immunogold analysis in monkeys. Neuroscience. 2005; 131(4):917-33. DOI: 10.1016/j.neuroscience.2004.12.004. View