Phox2b‐negative Parafacial Neurons Simultaneously Regulate Active Expiration and Airway Patency Under Hypercapnia in in situ Preparations of Rats

Abstract

Hypercapnia produces active expiration in rats and the recruitment of late‐expiratory (late‐E) neurons located in the parafacial Respiratory Group (pFRG) of the ventral medullary brainstem. We tested the hypothesis that hypercapnia produces active expiration and concomitant cranial respiratory motor responses controlling the oropharyngeal and upper airway patency by pFRG late‐E neurons disinhibition, but not via synaptic excitation. Phrenic nerve, abdominal nerve (AbN), cranial respiratory motor nerves, subglottal pressure, and medullary and spinal neurons/motoneurons were recorded in in situ preparations of juvenile rats. Hypercapnia evoked AbN active expiration (n=12), exaggerated late‐E discharges in cranial respiratory motor outflows (n=12), and glottal dilatation (n=6) via late‐E synaptic excitation of abdominal (n=8), hypoglossal (n=6) and laryngeal (n=12) motoneurons. Simultaneous rhythmic late‐E activity in previously silent Phox2b‐negative pFRG neurons was also evoked by hypercapnia (n=12). In addition, hypercapnia‐evoked AbN active expiration, neural and neuronal late‐E activities were eliminated by pFRG inhibition (n=18), but not after blockade of synaptic excitation (n=9). On the other hand, pFRG inhibition did not affect either hypercapnia‐induced inspiratory increases in respiratory motor outflows (n=12) or CO2 sensitivity of the more medial Phox2b‐positive neurons in the retrotrapezoid nucleus (RTN; n=8), despite elimination of AbN active expiration. Our data suggest that neither RTN Phox2b‐positive nor other CO2‐sensitive brainstem neurons activate Phox2b‐negative pFRG late‐E neurons under hypercapnia to produce AbN active expiration and concomitant cranial motor respiratory responses controlling the oropharyngeal and upper airway patency. Hypercapnia seems to produce pFRG late‐E neuronal disinhibition in in situ preparations of juvenile rats to activate abdominal, hypoglossal and laryngeal motoneurons.Support or Funding InformationFAPESP: SÃO PAULO RESEARCH FOUNDATION