Activation of metabotropic glutamate receptor 1 inhibits glutamatergic transmission in the substantia nigra pars reticulata

The substantia nigra pars reticulata is a primary output nucleus of the bas al ganglia motor circuit and is controlled by a fine balance between excita tory and inhibitory inputs. The major excitatory input to GABAergic neurons in the substantia ni.-ra arises from glutamatergic neurons in the subthala mic nucleus, whereas inhibitory inputs arise mainly from the striatum and t he globus pallidus. Anatomical studies revealed that metabotropic glutamate receptors (mGluRs) are highly expressed throughout the basal ganglia. Inte restingly, mRNA for group I mGluRs are abundant in neurons of the subthalam ic nucleus and the substantia nigra pars reticulata. Thus, it is possible t hat group I mGluRs play a role in the modulation of glutamatergic synaptic transmission at excitatory subthalamonigral synapses. To test this hypothes is, we investigated the effects of group I mGluR activation on excitatory s ynaptic transmission in putative GABAergic neurons in the substantia nigra pars reticulata using the whole cell patch clamp recording approach in slic es of rat midbrain. We report that activation of group I mGluRs by the sele ctive agonist (R, S)-3,5-dihydroxyphenylglycine (100 muM) decreases synapti c transmission at excitatory synapses in the substantia nigra pars reticula ta. This effect is selectively mediated by presynaptic activation of the gr oup I mGluR subtype, mGluR1. Consistent with these data, electron microscop ic immunocytochemical studies demonstrate the localization of mGluR1 a at p resynaptic sites in the rat substantia nigra pars reticulata. From this finding that group I mGluRs modulate the major excitatory inputs to GABAergic neurons in the substantia nigra pars reticulata we suggest tha t these receptors may play an important role in basal ganglia functions. St udying this effect, therefore, provides new insights into the modulatory ro le of glutamate in basal ganglia output nuclei in physiological and pathoph ysiological conditions. (C) 2001 IBRO. Published by Elsevier Science Ltd. A ll rights reserved.