Functional characterization and expression of thalamic GABAB receptors in a rodent model of Parkinson's disease

Groote, Carmen de; Wüllner, Ullrich; Pa, Löschmann; Luiten, P.G.M.; Klockgether, Thomas

doi:10.1016/s0028-3908(99)00125-2

Cited by 18 publications

(4 citation statements)

References 42 publications

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“…While an increase in the expression of GABA-B receptors in the parkinsonian state could account for this difference, the available evidence indicates either no change (current report, and de Groote et al, 1999) or even a downregulation of GPe GABA-B receptors binding (Calon et al, 2003) in parkinsonism. Alternatively, the coupling of these receptors to G-protein effectors or their assembly to auxiliary units (Schwenk et al, 2010) could be potentiated after dopamine depletion, resulting in enhanced responses to activation.…”

Section: Discussioncontrasting

confidence: 50%

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

Galván

Smith

et al. 2011

Experimental Neurology

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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.

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Section: Discussioncontrasting

confidence: 50%

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

Galván

Smith

et al. 2011

Experimental Neurology

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“…The possibility that thalamic GABA B receptors play a role in PD is supported by results showing that the GABA B agonist baclofen induces akinesia when administrated locally in the ventromedial (VM) nucleus of the thalamus (DiChiara et al, 1979; Klockgether et al, 1986; Wullner et al, 1987). However, blockade of GABA B receptors in the VM of unilatelarally 6‐hydroxydopamine‐lesioned rats does not have any effects on rotational behavior (de Groote et al, 1999), and binding studies could not find any significant changes in the number of GABA B binding sites in the thalamic ventral motor nuclei of MPTP‐treated parkinsonian monkeys (Calon et al, 2000). Modulation of glutamatergic neurotransmission has beneficial effects in PD.…”

Section: Discussionmentioning

confidence: 99%

GABA_B receptors in the centromedian/parafascicular thalamic nuclear complex: An ultrastructural analysis of GABA_BR1 and GABA_BR2 in the monkey thalamus

Villalba

Raju

Hall

et al. 2006

J of Comparative Neurology

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Strong gamma-aminobutyric acid type B (GABA(B)) receptor binding has been shown throughout the thalamus, but the distribution of the two GABA(B) receptor subunits, GABA(B) receptor subunit 1 (GABA(B)R1) and GABA(B) receptor subunit 2 (GABA(B)R2), remains poorly characterized. In primates, the caudal intralaminar nuclei, centromedian and parafascicular (CM/PF), are an integral part of basal ganglia circuits and a main source of inputs to the striatum. In this study, we analyzed the subcellular and subsynaptic distribution of GABA(B) receptor subunits by using light and electron microscopic immunocytochemical techniques. Quantitative immunoperoxidase and immunogold analysis showed that both subunits display a similar pattern of distribution in CM/PF, being expressed largely at extrasynaptic and perisynaptic sites in neuronal cell bodies, dendrites, and axon-like processes and less abundantly in axon terminals. Postsynaptic GABA(B)R1 labeling was found mostly on the plasma membrane (70-80%), whereas GABA(B)R2 was more evenly distributed between the plasma membrane and intracellular compartments of CM/PF neurons. A few axon terminals forming symmetric and asymmetric synapses were also labeled for GABA(B)R1 and GABA(B)R2, but the bulk of presynaptic labeling was expressed in small axon-like processes. About 20% of presynaptic vesicle-containing dendrites of local circuit neurons displayed GABA(B)R1/R2 immunoreactivity. Vesicular glutamate transporters (vGluT1)-containing terminals forming asymmetric synapses expressed GABA(B)R1 and/or displayed postsynaptic GABA(B)R1 at the edges of their asymmetric specialization. Overall, these findings provide evidence for multiple sites where GABA(B) receptors could modulate GABAergic and glutamatergic transmission in the primate CM/PF complex.

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“…Similarly, changes in trafficking may produce the sensitized response to GABA B signalling that is seen in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated monkeys (Galvan et al ., ), as no increases in GABA B receptor expression have been noted in human patients with PD (de Groote et al ., ) or MPTP‐treated monkeys (Galvan et al ., ). It is tempting to speculate that the minority of GPe neurons that display a significant outward postsynaptic current in response to baclofen in the healthy state (Chen et al ., ) corresponds to the Npas1 + GPe neuron population (Hernandez et al ., ), and that the decrease in pacemaking of GPe neurons seen in 6‐OHDA‐lesioned mice (Chan et al ., ; Hernandez et al ., ) may be attributable to a sensitized GABA B response.…”

Section: Synaptic and Neuromodulatory Control Of The Gpementioning

confidence: 97%

The external globus pallidus: progress and perspectives

Hegeman

Hong

Hernández

et al. 2016

Eur J of Neuroscience

132

154

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The external globus pallidus (GPe) of the basal ganglia is in a unique and powerful position to influence processing of motor information by virtue of its widespread projections to all basal ganglia nuclei. Despite the clinical importance of the GPe in common motor disorders such as Parkinson’s disease, we have only limited information about its cellular composition and organizational principles. In this review, we describe recent advances in our understanding of the diversity in the molecular profile, anatomy, physiology, and corresponding behavior during movement of GPe neurons. Importantly, we attempt to build consensus and highlight commonalities of the cellular classification based on existing but contentious literature. Additionally, we provide an analysis of the literature concerning the intricate reciprocal loops formed between the GPe and major synaptic partners, including both the striatum and the subthalamic nucleus. In conclusion, the GPe has emerged as a crucial node in the basal ganglia macrocircuit. While subtleties in the cellular makeup and synaptic connection of the GPe create new challenges, modern research tools have shown promise in untangling such complexity and will provide better understanding of the roles of the GPe in encoding movements and their associated pathologies.

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Functional characterization and expression of thalamic GABAB receptors in a rodent model of Parkinson's disease

Cited by 18 publications

References 42 publications

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

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

GABA_B receptors in the centromedian/parafascicular thalamic nuclear complex: An ultrastructural analysis of GABA_BR1 and GABA_BR2 in the monkey thalamus

The external globus pallidus: progress and perspectives

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Functional characterization and expression of thalamic GABAB receptors in a rodent model of Parkinson's disease

Cited by 18 publications

References 42 publications

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

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

GABAB receptors in the centromedian/parafascicular thalamic nuclear complex: An ultrastructural analysis of GABABR1 and GABABR2 in the monkey thalamus

The external globus pallidus: progress and perspectives

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GABA_B receptors in the centromedian/parafascicular thalamic nuclear complex: An ultrastructural analysis of GABA_BR1 and GABA_BR2 in the monkey thalamus