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PMID: 11549710 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Activation of group I metabotropic glutamate receptors produces a direct excitation and disinhibition of GABAergic projection neurons in the substantia nigra pars reticulata.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 21 ·No. 18 ·2001-09-15 ·Pages 7001-12

Marino MJ, Wittmann M, Bradley SR, Hubert GW, Smith Y, Conn PJ

Abstract

A pathological increase in excitatory glutamatergic input to substantia nigra pars reticulata (SNr) from the subthalamic nucleus (STN) is believed to play a key role in the pathophysiology of Parkinson's disease. We present an analysis of the physiological roles that group I metabotropic glutamate receptors (mGluRs) play in regulating SNr functions. Immunocytochemical analysis at the light and electron microscopic levels reveal that both mGuR1a and mGluR5 are localized postsynaptically in the SNr. Consistent with this, activation of group I mGluRs depolarizes SNr GABAergic neurons. Interestingly, although both group I mGluRs (mGluR1 and mGluR5) are expressed in these neurons, the effect is mediated solely by mGluR1. Light presynaptic staining for mGluR1a and mGluR5 was also observed in some terminals forming symmetric synapses and in small unmyelinated axons. Consistent with this, activation of presynaptic mGluR1a and mGluR5 decreases inhibitory transmission in the SNr. The combination of direct excitatory effects and disinhibition induced by activation of group I mGluRs could lead to a large excitation of SNr projection neurons. This suggests that group I mGluRs are likely to play an important role in the powerful excitatory control that the STN exerts on basal ganglia output neurons.

MeSH Terms
Animals Antibody Specificity Dose-Response Relationship, Drug Excitatory Amino Acid Agonists/pharmacology Excitatory Amino Acid Antagonists/pharmacology Excitatory Postsynaptic Potentials/physiology Immunohistochemistry In Vitro Techniques Male Membrane Potentials/drug effects,physiology Neural Inhibition/drug effects,physiology Neurons/drug effects,metabolism Organ Specificity Patch-Clamp Techniques Rats Rats, Sprague-Dawley Receptor, Metabotropic Glutamate 5 Receptors, Metabotropic Glutamate/antagonists & inhibitors,metabolism Substantia Nigra/cytology,drug effects,metabolism Synaptic Transmission/drug effects,physiology Tetrodotoxin/pharmacology gamma-Aminobutyric Acid/metabolism
Chemicals
Excitatory Amino Acid Agonists Excitatory Amino Acid Antagonists Grm5 protein, rat Receptor, Metabotropic Glutamate 5 Receptors, Metabotropic Glutamate metabotropic glutamate receptor type 1 Tetrodotoxin gamma-Aminobutyric Acid
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Marino M J
Department of Pharmacology and Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 30322, USA.
Wittmann M
Bradley S R
Hubert G W
Smith Y
Conn P J
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2001-09-15
Pages
7001-12
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6762993
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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