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

Marino MJ, Wittmann M, Bradley SR, Hubert GW, Smith Y, Conn PJ
J Neurosci. 2001 21 (18): 7001-12

PMID: 11549710

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 (22)

Animals Antibody Specificity Dose-Response Relationship, Drug Excitatory Amino Acid Agonists Excitatory Amino Acid Antagonists Excitatory Postsynaptic Potentials gamma-Aminobutyric Acid Immunohistochemistry In Vitro Techniques Male Membrane Potentials Neural Inhibition Neurons Organ Specificity Patch-Clamp Techniques Rats Rats, Sprague-Dawley Receptor, Metabotropic Glutamate 5 Receptors, Metabotropic Glutamate Substantia Nigra Synaptic Transmission Tetrodotoxin

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