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Modulation of rhythmic patterns and cumulative depolarization by group I metabotropic glutamate receptors in the neonatal rat spinal cord in vitro


: Professor A. Nistri, as above.


The role of group I metabotropic glutamate receptors (mGluRs), and their subtypes 1 or 5, in rhythmic patterns generated by the neonatal rat spinal cord was investigated. Fictive locomotor patterns induced by N-methyl-d-aspartate + serotonin were slowed down by the subtype 1 antagonists (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) or 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) and unaffected by the subtype 5 antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP). The group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) depolarized ventral roots and disrupted fictive locomotion, an effect blocked by AIDA (or CPCCOEt) and reversed by increasing the N-methyl-d-aspartate concentration. Cumulative depolarization induced by low frequency trains of dorsal root stimuli was attenuated by DHPG and unchanged by AIDA or MPEP while rhythmic patterns or motoneuron spike wind-up persisted. Disinhibited bursting induced by strychnine + bicuculline was accelerated by DHPG, slowed down by AIDA (which prevented the action of DHPG), unaffected by MPEP and counteracted by the selective group II agonist (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine. The DHPG transformed regular bursting into arrhythmic bursting, a phenomenon also produced by the group II mGluR antagonist (2S)-α-ethylglutamic acid. These results indicate that, during fictive locomotion or disinhibited bursting, endogenous glutamate could activate discrete clusters of subtype 1 mGluRs to facilitate discharges. Diffuse activation by the exogenous agonist DHPG of group I mGluRs throughout spinal networks had an excitatory effect overshadowed by its much stronger depressant action due to concomitant facilitation of glycinergic transmission. Irregular disinhibited bursting caused by activation of subtype 1 receptors or block of group II receptors suggests that mGluRs could control not only the frequency but also the periodicity of bursting patterns, outlining novel mechanisms contributing to burst duration.