RT Journal Article SR Electronic T1 Interaction between Metabotropic and Ionotropic Glutamate Receptors Regulates Neuronal Network Activity JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 5382 OP 5391 DO 10.1523/JNEUROSCI.20-14-05382.2000 VO 20 IS 14 A1 Patrik Krieger A1 Jeanette Hellgren-Kotaleski A1 Petronella Kettunen A1 Abdel Jabbar El Manira YR 2000 UL http://www.jneurosci.org/content/20/14/5382.abstract AB Experimental and computational techniques have been used to investigate the group I metabotropic glutamate receptor (mGluR)-mediated increase in the frequency of spinal cord network activity underlying locomotion in the lamprey. Group I mGluR activation potentiated the amplitude of NMDA-induced currents in identified motoneurons and crossed caudally projecting network interneurons. Group I mGluRs also potentiated NMDA-induced calcium responses. This effect was blocked by a group I mGluR-specific antagonist, but not by blockers of protein kinase A, C, or G. The effect of group I mGluRs activation was also tested on NMDA-induced oscillations known to occur during fictive locomotion. Activation of these receptors increased the duration of the plateau phase and decreased the duration of the hyperpolarizing phase. These effects were blocked by a group I mGluR antagonist. To determine its role in the modulation of NMDA-induced oscillations and the locomotor burst frequency, the potentiation of NMDA receptors by mGluRs was simulated using computational 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 rhythm.Our results thus show a postsynaptic interaction between group I mGluRs and NMDA receptors in lamprey spinal cord neurons, which can account for the regulation of the locomotor network output by mGluRs.