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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
Author(s) -
Taccola Giuliano,
Marchetti Cristina,
Nistri Andrea
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.0953-816x.2003.03148.x
Subject(s) - metabotropic glutamate receptor , metabotropic receptor , bicuculline , chemistry , agonist , bursting , neuroscience , glutamate receptor , pharmacology , gaba receptor antagonist , excitatory postsynaptic potential , antagonist , biophysics , receptor , biochemistry , biology
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 (2 S ,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 (2 S )‐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.