Interaction between metabotropic and ionotropic glutamate receptors regulates neuronal network activity

Experimental and computational techniques have been used to investigate the group I metabotropic glutamate receptor (mGluR)-mediated increase in the f requency of spinal cord network activity underlying locomotion in the lampr ey. Group I mGluR activation potentiated the amplitude of NMDA-induced curr ents in identified motoneurons and crossed caudally projecting network inte rneurons. Group I mGluRs also potentiated NMDA-induced calcium responses. T his effect was blocked by a group I mGluR-specific antagonist, but not by b lockers of protein kinase A, C, or G. The effect of group I mGluRs activati on was also tested on NMDA-induced oscillations known to occur during ficti ve locomotion. Activation of these receptors increased the duration of the plateau phase and decreased the duration of the hyperpolarizing phase. Thes e effects were blocked by a group I mGluR antagonist. To determine its role in the modulation of NMDA-induced oscillations and the locomotor burst fre quency, the potentiation of NMDA receptors by mGluRs was simulated using co mputational techniques. Simulating the interaction between these receptors reproduced the modulation of the plateau and hyperpolarized phases of NMDA- induced oscillations, and the increase in the frequency of the locomotor rh ythm. Our results thus show a postsynaptic interaction between group I mGluRs and NMDA receptors in lamprey spinal cord neurons, which can account for the r egulation of the locomotor network output by mGluRs.