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The Journal of Neurophysiology Vol. 85 No. 5 May 2001, pp. 1960-1968
Copyright ©2001 by the American Physiological Society
Department of Pharmacology, Emory University, Atlanta, Georgia 30322
Wittmann, Marion,
Michael J. Marino,
Stefania Risso Bradley, and
P. Jeffrey Conn.
Activation of Group III mGluRs Inhibits GABAergic and
Glutamatergic Transmission in the Substantia Nigra Pars
Reticulata. J. Neurophysiol. 85: 1960-1968, 2001. The
GABAergic projection neurons of the substantia nigra pars
reticulata (SNr) exert an important influence on the initiation and
control of movement. The SNr is a primary output nucleus of the basal
ganglia (BG) and is controlled by excitatory inputs from the
subthalamic nucleus (STN) and inhibitory inputs from the striatum and
globus pallidus. Changes in the output of the SNr are believed to be
critically involved in the development of a variety of movement
disorders. Anatomical studies reveal that metabotropic glutamate
receptors (mGluRs) are highly expressed throughout the BG.
Interestingly, mRNA for group III mGluRs are highly expressed in STN,
striatum, and globus pallidus, and immunocytochemical studies have
shown that the group III mGluR proteins are present in the SNr. Thus it
is possible that group III mGluRs play a role in the modulation of
synaptic transmission in this nucleus. We performed whole cell
patch-clamp recordings from nondopaminergic SNr neurons to investigate
the effect of group III mGluR activation on excitatory and inhibitory
transmission in the SNr. We report that activation of group III mGluRs
by the selective agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4, 100 µM) decreases inhibitory synaptic
transmission in the SNr. Miniature inhibitory postsynaptic currents
studies and paired-pulse studies reveal that this effect is mediated by a presynaptic mechanism. Furthermore we found that L-AP4
(500 µM) also reduces excitatory synaptic transmission at the STN-SNr synapse by action on presynaptically localized group III mGluRs. The
finding that mGluRs modulate the major inputs to SNr neurons suggests
that these receptors may play an important role in motor function and
could provide new targets for the development of pharmacological
treatments of movement disorders.
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