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The Journal of Neuroscience, September 15, 2001, 21(18):7001-7012
Activation of Group I Metabotropic Glutamate Receptors Produces a Direct Excitation and Disinhibition of GABAergic Projection Neurons in the Substantia Nigra Pars Reticulata
Michael J. Marino1, Marion Wittmann4, Stefania Risso Bradley1, George W. Hubert2, Yoland Smith2, and P. Jeffrey Conn3 Departments of 1 Pharmacology and 2 Neurology and Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 30322, 3 Merck Research Laboratories, West Point, Pennsylvania 19486, and 4 Tierphysiologie, University of Tuebingen, D-72076 Tuebingen, Germany
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.
Key words: substantia nigra pars reticulata; group I metabotropic glutamate receptors; movement disorders; slow excitatory postsynaptic potential; disinhibition; basal ganglia output nucleus
Copyright © 2001 Society for Neuroscience 0270-6474/01/21187001-12$05.00/0
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