Roles of n-methyl-d-aspartate (NMDA) and non-NMDA receptors in the mediation of excitatory inputs to inspiratory bulbospinal neurons in dogs

The relative roles of ionotropic non-NMDA and NMDA receptors in supplying excitatory drive to inspiratory bulbospinal neurons (IBSNs) of the ventral respiratory group were studied In anesthetized, ventilated, paralyzed and vagotomized dogs. Multibarrel micropipettes were used to simultaneously record single unit neuronal activity and picoeject the NMDA antagonist, 2-amino-5-phosphonopentanoate (AP5; 2 mM), the non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f) quinoxaline (NBQX; 0.25 mM), and the artificial cerebrospinal fluid vehicle. Ejected volume-rates were directly measured via meniscus level changes. Plots of steady-state, peak spontaneous IBSN discharge frequency (F_n) vs. dose-rate were used to determine the minimum dose for near maximal reduction in F_n. Preliminary results indicate that both AP5 and NBQX produce strong, dose-dependent, decreases in F_n. The average maximum reduction produced by APS was 60.7±19.7% (167±81 pmol/min) and by NBQX was 46.7±7.4% (16.9±4.9 pmol/min) The selectivity of these antagonists was verified via their ability to antagonize excitation induced by their specific agonists NMDA and a-amino-3hydroxy-5-methyl-4-isoxazole-4-propionlc acid (AMPA). These results suggest that most of the excitatory drive to IBSNs is mediated by both NMDA and non-NMDA glutamate receptors, unlike the excitatory drive to expiratory bulbospinal neurons which is mainly dependent on NMDA receptors alone.