Differential roles of ionotropic glutamate receptors in canine medullary inspiratory neurons of the ventral respiratory group

Differential roles of ionotropic glutamate receptors in canine medullary in spiratory neurons of the ventral respiratory group. J. Neurophysiol. 82: 60 -68, 1999. The relative roles of ionotropic N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in supplying excitatory drive to inspiratory (I) augmenting pattern neurons of the ventral respiratory group were studie d in anesthetized, ventilated, paralyzed, and vagotomized dogs. Multibarrel micropipettes were used to record simultaneously single-unit neuronal acti vity and pressure microeject the NMDA antagonist, 2-amino-5-phosphonovalera te (AP5; 2 mM), the non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-b enzo(f)quinoxaline (NBQX; 0.25 mM), and an artificial cerebrospinal fluid v ehicle. Ejected volume-rates were measured directly via meniscus level chan ges. The moving time average of phrenic nerve activity was used to determin e respiratory phase durations and to synchronize cycle-triggered histograms of the discharge patterns. Both AP5 and NBQX produced dose-dependent reduc tions in peak spontaneous I neuronal discharge frequency (F-n). The average (+/- SE) maximum reduction in peak F-n produced by AP5 was 69.1 +/- 4.2% a nd by NBQX was 47.1 +/- 3.3%. Blockade of both,glutamate receptor subtypes nearly silenced these neurons, suggesting that their activity is highly dep endent on excitatory synaptic drive mediated by ionotropic glutamate recept ors. Differential effects were found for the two glutamatergic antagonists. AP5 produced downward, parallel shifts in the augmenting pattern of discha rge, whereas NBQX reduced the slope of the augmenting discharge pattern. Th ese results suggest that time-varying excitatory input patterns to the cani ne I bulbospinal neurons are mediated by non-NMDA glutamate receptors and t hat constant or tonic input patterns to these neurons are mediated by NMDA receptors.