Ablation of vagal preganglionic neurons innervating the extra-thoracic trachea affects ventilatory responses to hypercapnia and hypoxia

This study tested the hypothesis that during hypercapnia or hypoxia, airway-related vagal preganglionic neurons (AVPNs) of the nucleus ambiguus (NA) release acetylcholine (ACh), which in a paracrine fashion, activates ACh receptors expressed by inspiratory rhythm generating cells. AVPNs in the NA were ablated by injecting a saporin- (SA) cholera toxin b subunit (CTb-SA) conjugate into the extra-thoracic trachea (n = 6). Control animals were injected with free CTb (n = 6). In CTb treated rats, baseline ventilation and ventilatory responses to hypercapnia (5 and 12% CO2 in O2) or hypoxia (8% O2 in N2) were similar (p > 0.05) prior to and 5 days after injection. CTb-SA injected rats maintained rhythmic breathing patterns 5 days post injection, however, tachypneic responses to hypercapnia or hypoxia were significantly reduced. The number of choline acetyltransferase (ChAT) immunoreactive cells in the NA was much lower (p < 0.05) in CTb-SA rats as compared to animals receiving CTb only. These results suggest that AVPNs participate in the respiratory frequency response to hypercapnia or hypoxia.