Inhibitory synaptic mechanisms regulating upper airway patency.

Abstract

The breathing cycle of vertebrates comprises three phases (inspiration, postinspiration and expiration) that are apparent in the activities generated in the ponto-medullary respiratory network. A large body of evidence now indicates that in adult mammals generation of this three-phase pattern is based on reciprocal synaptic inhibition between distinct subsets of respiratory neurones. This review summarises our recent experiments focused on the role of glycinergic inhibition in respiratory pattern formation: e.g. in co-ordinating the activity of spinal and cranial motor outputs that drive the ventilatory pump (thoracic and abdominal muscles) and adjust airflow by regulating laryngeal resistance (laryngeal abductors and adductors). We used arterially perfused in situ preparations of neonatal and mature rat and show that specific blockade of glycine receptors within the ponto-medullary network caused a severe disruption of the co-ordination of spinal and cranial motor outputs: postinspiratory neurones lose their characteristic inspiratory inhibition revealing excitatory synaptic drive coincident with inspiratory phrenic nerve activity. The resulting simultaneous discharge of inspiratory and postinspiratory neurones caused co-activation of both glottal abductors and adductors during neural inspiration. The latter resulted in a paradoxical inspiratory adduction of the vocal fold and severe disruption of the eupneic breathing pattern. The effect of blocking glycine receptors was the same in both mature and newborn rats suggesting that glycinergic inhibition is essential for co-ordinating cranial and spinal motor outputs from birth.