The brainstem network involved in coordination of inspiratory activity and cholinergic outflow to the airways

The respiratory rhythm modulates cholinergic outflow to the tracheal smooth muscle through the parasympathetic nerves. To determine the basis of this modulation, we combined the retrograde tracer technique to identify bulbospinal cells projecting to phrenic motoneurons, and the transneuronal labeling method to visualize medullary neurons that innervate airway-related vagal preganglionic cells. Following injections of fluorogold into the ventral horns of the cervical spinal cord and injections of pseudorabies virus (PRV) into the wall of the extrathoracic trachea of superior cervical ganglioctomized Sprague-Dawley rats. A large number of the double-labeled cells were identified along the ventral aspect of the medulla oblongata. Most frequently, double-labeled neurons were seen in the medial tegmental field, particularly in the parapyramidal region, within the gigantocellular nuclei, and the caudal raphe nuclei. Less frequently, double-labeled neurons were found in the ventrolateral medulla. No double-labeled cell was observed in the dorsal aspect of the medulla oblongata. This study indicates that a subset of medullary neurons that project to phrenic motoneurons also innervate the airway-related vagal preganglionic cells, allowing the coupling of inspiratory activity and parasympathetic outflow to the airways.