Phasic vagal sensory feedback transforms respiratory neuron activity in vitro

Abstract

The isolated neonatal rat medulla generates respiratory-related rhythms recorded from cervical spinal cord ventral roots. When lungs and their vagal innervation are retained, respiratory activity is modulated by lung mechanoreceptor feedback: transient lung inflation triggered off inspiratory onset (phasic inflation) shortens inspiration and increases respiratory frequency. In this study, the activity of six respiratory neuron classes before and during phasic inflation was studied. Type 1 and 2 inspiratory neurons, identified in the transverse slice, were distinguished by the presence of a transient outward current or a hyperpolarization-activated inward current, respectively. Cell types only identified in the en bloc medulla included type II and III inspiratory neurons, distinguished by delayed onset and peri-inspiratory inhibition, respectively, and preinspiratory neurons, active before and after but silent during inspiration. Biphasic neurons, identified in the preparation used here, fired briskly during lung inflation but are otherwise quiescent. During phasic inflation, biphasic neurons showed a decrementing expiratory pattern of activity, matched by augmented postinspiratory hyperpolarization in type 1 neurons only, suggesting that biphasic neurons inhibit type 1 neurons, removing drive to other inspiratory neurons and terminating the inspiratory burst. This mechanism could account for a phasic inflation-induced increase in respiratory frequency via resetting effects. Alternatively, the phasic inflation-induced respiratory frequency increase may be attributable to slow facilitation. Slow modulation consistent with facilitation was apparent in the earlier onset of pre-I firing before inspiration and loss of postinspiratory firing and in the earlier onset of depolarization in type 2 neurons. On the basis of relative onset times and responses to phasic inflation, connectivity between these cell types is proposed.