Regulation of substantia nigra pars reticulata neuronal activity by excitatory amino acids

Midbrain non-dopaminergic neurons of the substantia nigra pars reticulata play an important role in the basal ganglia circuitry. The regulation of their electrical activity by excitatory amino acid (EAA) inputs was investigated using in vivo electrophysiological methods in chloral hydrate-anaesthetized rats. We first determined the subtypes of EAA receptors present on reticulata neurons, using microiontophoretic application of selective agonists: kainic acid (KA), (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), N-methyl-D-aspartic acid (NMDA), and trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD). Each agonist activated reticulata neurons and the apparent rank order of efficacy was: KA> or =AMPA=NMDA>trans-ACPD. Using pressure or iontophoretic microejections of ionotropic and metabotropic receptor antagonists, we then investigated EAA receptor subtypes involved in the spontaneous firing rate of reticulata neurons. Kynurenic acid and (+/-)-2-amino-5-phosphonopentanoic acid (AP-5) markedly decreased the spontaneous firing rate of reticulata neurons, while 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) was much less effective. The metabotropic receptor antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) failed to affect the spontaneous electrical activity. In contrast to CNQX, microapplications of AP-5 sometimes produced total inhibition. This powerful effect may reflect the potential importance of NMDA receptors in regulating the activity of some reticulata neurons. These results indicate that both functional ionotropic (NMDA and non-NMDA) and metabotropic EAA receptors are present on non-dopaminergic substantia nigra pars reticulata neurons. Moreover, in the anaesthetized animal, the spontaneous firing rate of these neurons, mediated by EAA inputs, seems mainly due to the tonic activation of ionotropic, but not metabotropic, receptors.