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 disinhibition of pFRG late-E neurons, 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, exaggerated late-E discharges in cranial respiratory motor outflows, and glottal dilatation via late-E synaptic excitation of abdominal, hypoglossal and laryngeal motoneurons. Simultaneous rhythmic late-E activity in previously silent pFRG neurons, which did not express the marker of ventral medullary CO -sensitive neurons (transcription factor Phox2b), was also evoked by hypercapnia. In addition, hypercapnia-evoked AbN active expiration, neural and neuronal late-E activities were eliminated by pFRG inhibition, but not after blockade of synaptic excitation. On the other hand, pFRG inhibition did not affect either hypercapnia-induced inspiratory increases in respiratory motor outflows or CO sensitivity of the more medial Phox2b-positive neurons in the retrotrapezoid nucleus (RTN). Our data suggest that neither RTN Phox2b-positive nor other CO -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 produces disinhibition of non-chemosensitive pFRG late-E neurons in in situ preparations of juvenile rats to activate abdominal, hypoglossal and laryngeal motoneurons.
New Findings What is the central question of this study?Does the parafacial respiratory group (pFRG), which mediates active expiration, recruit nasofacial and oral motoneurons to coordinate motor activities that engage muscles controlling airways in rats during active expiration. What is the main finding and its importance?Hypercapnia/acidosis or pFRG activation evoked active expiration and stimulated the motoneurons and nerves responsible for the control of nasofacial and oral airways patency simultaneously. Bilateral pFRG inhibition abolished active expiration and the simultaneous nasofacial and oral motor activities induced by hypercapnia/acidosis. The pFRG is more than a rhythmic oscillator for expiratory pump muscles: it also coordinates nasofacial and oral motor commands that engage muscles controlling airways. Abstract Active expiration is mediated by an expiratory oscillator located in the parafacial respiratory group (pFRG). Active expiration requires more than contracting expiratory muscles as multiple cranial nerves are recruited to stabilize the naso‐ and oropharyngeal airways. We tested the hypothesis that activation of the pFRG recruits facial and trigeminal motoneurons to coordinate nasofacial and oral motor activities that engage muscles controlling airways in rats during active expiration. Using a combination of electrophysiological and pharmacological approaches, we identified brainstem circuits that phase‐lock active expiration, nasofacial and oral motor outputs in an in situ preparation of rat. We found that either high chemical drive (hypercapnia/acidosis) or unilateral excitation (glutamate microinjection) of the pFRG evoked active expiration and stimulated motoneurons (facial and trigeminal) and motor nerves responsible for the control of nasofacial (buccal and zygomatic branches of the facial nerve) and oral (mylohyoid nerve) motor outputs simultaneously. Bilateral pharmacological inhibition (GABAergic and glycinergic receptor activation) of the pFRG abolished active expiration and the simultaneous nasofacial and oral motor activities induced by hypercapnia/acidosis. We conclude that the pFRG provides the excitatory drive to phase‐lock rhythmic nasofacial and oral motor circuits during active expiration in rats. Therefore, the pFRG is more than a rhythmic oscillator for expiratory pump muscles: it also coordinates nasofacial and oral motor commands that engage muscles controlling airways in rats during active expiration.
During rest, inspiration is an active phenomenon, whereas expiration is passive. Under conditions of high chemical drive, such as hypercapnia/acidosis, there is an increase in inspiratory activity, expiration becomes active and upper airway resistance is reduced. The locus coeruleus noradrenergic neurons (A6 neurons) are activated when exposed to elevated CO 2 /[H + ] levels and modulate respiratory brainstem neurons regulating ventilation. However, the role of A6 neurons in the control of upper airway resistance is not fully understood. We tested the hypothesis that A6 neurons contribute to the central generation of active inspiratory and expiratory responses and the associated changes in the motor nerves controlling upper airway resistance during hypercapnia/acidosis in rats. Using a perfused brainstem-spinal cord preparation, we inhibited A6 neurons using pharmacogenetics and evaluated the active expiratory (abdominal nerve), laryngeal (cervical vagus nerve), oropharyngeal (hypoglossal nerve) and inspiratory (phrenic nerve) motor nerve responses to hypercapnia/acidosis. Acute inhibition of A6 neurons did not produce significant changes in the respiratory pattern in normocapnia. However, the hypercapnia/acidosisinduced active expiratory response and the associated changes in the motor nerves responsible for control of oropharyngeal and laryngeal resistance, as well as the inspiratory response were all reduced after inhibition of A6 neurons. Our data demonstrate that A6 neurons exert an important excitatory synaptic drive to the central generation of both active inspiratory and expiratory activities and modulate the control of upper airway resistance during hypercapnia/acidosis.
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