Abstract
Distinct parasympathetic postganglionic neurons mediate contractions and relaxations of the guinea pig airways. We set out to characterize the vagal inputs that regulate contractile and relaxant airway parasympathetic postganglionic neurons. Single and dual retrograde neuronal tracing from the airways and esophagus revealed that distinct, but intermingled, subsets of neurons in the compact formation of the nucleus ambiguus (nAmb) innervate these two tissues. Tracheal and esophageal neurons identified in the nAmb were cholinergic. Esophageal projecting neurons also preferentially (greater than 70%) expressed the neuropeptide CGRP, but could not otherwise be distinguished immunohistochemically from tracheal projecting preganglionic neurons. Few tracheal or esophageal neurons were located in the dorsal motor nucleus of the vagus. Electrical stimulation of the vagi in vitro elicited stimulus dependent tracheal and esophageal contractions and tracheal relaxations. The voltage required to evoke tracheal smooth muscle relaxation was significantly higher than that required for evoking either tracheal contractions or esophageal longitudinal striated muscle contractions. Together our data support the hypothesis that distinct vagal preganglionic pathways regulate airway contractile and relaxant postganglionic neurons. The relaxant preganglionic neurons can also be differentiated from the vagal motor neurons that innervate the esophageal striated muscle.
Highlights
The guinea pig is commonly used as a model for studying the neural control of airway smooth muscle tone
Organization of vagal motor neurons in the nucleus ambiguus Cholinergic neurons in the guinea pig nAmb extended in a column from approximately 3 mm rostral to 3 mm caudal to the Obex (Figure 1A)
Retrograde tracing from the distal end of the cervical recurrent laryngeal nerve (RLN) labeled neurons only in the ipsilateral caudal nAmb neuronal pool (Figure 2B)
Summary
The guinea pig is commonly used as a model for studying the neural control of airway smooth muscle tone. The cholinergic contractile postganglionic neurons are located in intrinsic parasympathetic ganglia residing in or near the adventitial wall of the trachea and large airways (Baluk and Gabella, 1989; Canning and Undem, 1993; Myers, 2000; Mazzone and McGovern, 2010). Postganglionic neurons innervating the airways receive input from motor neurons via the recurrent laryngeal nerve (RLN) of the vagus (Baluk and Gabella, 1989; Canning and Undem, 1993). The brainstem organization of the vagal motor fibers contained in the guinea pig RLN is unknown as is the identity of the preganglionic neurons controlling airway contractile and relaxant responses. We hypothesize that brainstem topographical organization, neurochemical phenotype and functional attributes will distinguish distinct vagal subpopulations regulating airway contractile and relaxant responses
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