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

• Authors: Michael J. Marino, Emory University; Marion Wittmann, University of Tuebingen; Stefania Risso Bradley, Emory University; George W. Hubert, Emory University; Yoland Smith, Emory University; P. Jeffrey Conn, Merck Research Laboratories
• Journal Title: Journal of Neuroscience Nursing
• Volume: Volume 21, Number 18
• Publisher: Lippincott, Williams & Wilkins | 2001-09-15, Pages 7001-7012
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1523/JNEUROSCI.21-18-07001.2001
• Subjects: Biology, Neuroscience; Health Sciences, Pharmacology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Neurosciences; Neurosciences & Neurology; substantia nigra pars reticulata; group I metabotropic glutamate receptors; movement disorders; slow excitatory postsynaptic potential; disinhibition; basal ganglia output nucleus; RAT BASAL GANGLIA; PRIMATE SUBTHALAMIC NUCLEUS; CA3 PYRAMIDAL NEURONS; MESSENGER-RNA; IMMUNOHISTOCHEMICAL LOCALIZATION; SYNAPTIC TRANSMISSION; STRIATAL NEURONS; DOPAMINERGIC-NEURONS; GLOBUS-PALLIDUS; AREA CA1

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.