Down-regulation of metabotropic glutamate receptor 1α in globus pallidus and substantia nigra of parkinsonian monkeys

K. Kaneda, Y. Tachibana, M. Imanishi, Hitoshi Kita, R. Shigemoto, A. Nambu, M. Takada

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Enhanced glutamatergic neurotransmission via the subthalamopallidal or subthalamonigral projection seems crucial for developing parkinsonian motor signs. In the present study, the possible changes in the expression of metabotropic glutamate receptors (mGluRs) were examined in the basal ganglia of a primate model for Parkinson's disease. When the patterns of immunohistochemical localization of mGluRs in monkeys administered systemically with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were analysed in comparison with normal controls, we found that expression of mGluR1α, but not of other subtypes, was significantly reduced in the internal and external segments of the globus pallidus and the substantia nigra pars reticulata. To elucidate the functional role of mGluR1 in the control of pallidal neuron activity, extracellular unit recordings combined with intrapallidal microinjections of mGluR1-related agents were then performed in normal and parkinsonian monkeys. In normal awake conditions, the spontaneous firing rates of neurons in the pallidal complex were increased by DHPG, a selective agonist of group I mGluRs, whereas they were decreased by AIDA, a selective antagonist of group I mGluRs, or LY367385, a selective antagonist of mGluR1. These electrophysiological data strongly indicate that the excitatory mechanism of pallidal neurons by glutamate is mediated at least partly through mGluR1. The effects of the mGluR1-related agents on neuronal firing in the internal pallidal segment became rather obscure after MPTP treatment. Our results suggest that the specific down-regulation of pallidal and nigral mGluR1 ot in the parkinsonian state may exert a compensatory action to reverse the overactivity of the subthalamic nucleus-derived glutamatergic input that is generated in the disease.

Original languageEnglish (US)
Pages (from-to)3241-3254
Number of pages14
JournalEuropean Journal of Neuroscience
Volume22
Issue number12
DOIs
StatePublished - Dec 1 2005

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Globus Pallidus
Substantia Nigra
Haplorhini
Down-Regulation
Metabotropic Glutamate Receptors
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Neurons
alpha-methyl-4-carboxyphenylglycine
Subthalamic Nucleus
Microinjections
metabotropic glutamate receptor type 1
Basal Ganglia
Synaptic Transmission
Primates
Parkinson Disease
Glutamic Acid

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Down-regulation of metabotropic glutamate receptor 1α in globus pallidus and substantia nigra of parkinsonian monkeys. / Kaneda, K.; Tachibana, Y.; Imanishi, M.; Kita, Hitoshi; Shigemoto, R.; Nambu, A.; Takada, M.

In: European Journal of Neuroscience, Vol. 22, No. 12, 01.12.2005, p. 3241-3254.

Research output: Contribution to journalArticle

Kaneda, K. ; Tachibana, Y. ; Imanishi, M. ; Kita, Hitoshi ; Shigemoto, R. ; Nambu, A. ; Takada, M. / Down-regulation of metabotropic glutamate receptor 1α in globus pallidus and substantia nigra of parkinsonian monkeys. In: European Journal of Neuroscience. 2005 ; Vol. 22, No. 12. pp. 3241-3254.
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