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

Abstract

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)-alpha-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.

Intrinsic and Functional Differences among Commissural Interneurons during Fictive Locomotion and Serotonergic Modulation in the Neonatal Mouse

“…However, we cannot eliminate the possibility that 5-HT exerts its effects in part presynaptically, because ascending CINs have been shown recently to be excited by acetylcholine (Carlin et al, 2006), which we did not block. These neurons are also probably modulated by other metabotropic inputs [for example, metabotropic glutamatergic inputs (Taccola et al, 2003(Taccola et al, , 2004], although they have not yet been identified. In addition, in a few dCINs with most fast synaptic transmission blocked, serotonin evoked small oscillations resembling truncated action potentials; these were seen previously in aCINs (Zhong et al, 2006) in which we showed that they arise from electrical coupling to unidentified neurons.…”

Tuning and playing a motor rhythm: how metabotropic glutamate receptors orchestrate generation of motor patterns in the mammalian central nervous system

“…3A; Taccola et al 2004b). Disinhibited bursting occurs spontaneously via activation of network glutamatergic ionotropic receptors predominantly of the AMPA type, while NMDA receptors simply modulate this pattern (Bracci et al 1996).…”

“…C, conversely, fictive locomotor patterns brought below threshold by decreasing the 5-HT concentration are restored by adding a small (5 μM) dose of DHPG. Data are reproduced, with permission, from Taccola et al (2004b). D, fast inward current recorded (under voltage clamp, V) from single HM induced by puffer application (P) of AMPA is followed by rhythmic oscillations when occurring in coincidence with a concentration of DHPG (5 μM) subthreshold for oscillations.…”

“…3A). Furthermore, DHPG facilitates the alternating locomotor patterns associated with the network depolarization evoked by repeated DR stimuli (Taccola et al 2004b). Activation of group I mGluRs by endogenous glutamate during fictive locomotion is shown by lengthening of the locomotor cycle period by group I antagonists (Taccola et al 2004b).…”

A study of the potential neuroprotective effect of riluzole on locomotor networks of the neonatal rat spinal cord in vitro damaged by excitotoxicity

“…Signals were captured, digitized and analyzed with pClamp software (version 9.2; Molecular Devices, Sunnyvale, CA, USA). Afferent fibers of a single dorsal root (DR) were stimulated via a bipolar suction electrode with electrical stimuli applied every 60 s. The minimum intensity of the stimulus to induce a reflex response in the ipsilateral homosegmental VR was considered as the stimulation threshold (Taccola et al, 2004). Trains of DR stimuli (0.1-ms duration, 30 pulse trains at 2 Hz) were used to elicit cumulative depolarization with superimposed alternating oscillatory activity typical of fictive locomotion by P2x threshold pulses.…”