NMDA as well as non-NMDA receptors mediate the neurotransmission of inspiratory drive to phrenic motoneurons in the adult rat

Abstract

The neurotransmission of bulbospinal respiratory drive is believed to involve primarily non-NMDA receptors located in the phrenic motonucleus (PMN). This conclusion is based on studies carried out mainly on in vitro brainstem-spinal cord preparations of the neonatal rat. The present study was undertaken to investigate the transmitter/receptor mechanisms in the PMN which are involved in the neurotransmission of inspiratory drive, using an in vivo adult rat model. Microinjections of glutamate, NMDA and AMPA into the PMN elicited an increase in the phrenic nerve (PN) background discharge. These injections did not alter significantly the frequency of spontaneously occurring PN bursts confirming that mechanisms responsible for respiratory rhythm reside in the supraspinal structures. Microinjections of an NMDA receptor blocker (AP-7), in concentrations that did not alter the responses to a non-NMDA receptor agonist (AMPA), reduced the PN amplitude significantly. Similarly, microinjections of a potent non-NMDA receptor blocker (NBQX), in concentrations that did not alter responses to NMDA, reduced the PN amplitude significantly. Sequential microinjections, within an interval of 5 min, of AP-7 and NBQX into the PMN, resulted in a dramatic reduction in the spontaneous PN bursts. The reduction of PN amplitude started immediately after the microinjection of AP-7 and NBQX, either alone or in combination, and reached a maximum within 5-10 min. These results indicate that, unlike in the neonatal rat, both NMDA and non-NMDA receptors located in the PMN play a significant role in the neurotransmission of the inspiratory drive in the adult rat.