An essential component to brainstem cough gating identified in anesthetized guinea pigs

Coughing protects and clears the airways and lungs of inhaled irritants, particulates, pathogens, and accumulated secretions. An initial urge to cough, and an almost binary output suggests gating mechanisms that encode and modulate this defensive reflex. Whether this "gate" has a physical location for the physiological barrier it poses to cough is unknown. Here we describe a critical component to cough gating, the central terminations of the cough receptors. A novel microinjection strategy defined coordinates for microinjection of glutamate receptor antagonists that nearly abolished cough evoked from the trachea and larynx in anesthetized guinea pigs while having no effect on basal respiratory rate and little or no effect on reflexes attributed to activating other afferent nerve subtypes. Comparable microinjections in adjacent brainstem locations (0.5-2 mm distal) were without effect on coughing. Subsequent transganglionic and dual tracing studies confirmed that the central terminations of the cough receptors and their primary relay neurons are found bilaterally within nucleus tractus solitarius (nTS), lateral to the commissural subnucleus and perhaps in the medial subnuclei. These synapses possess the physiological characteristics of a cough gate. Their localization should facilitate more mechanistic studies of the encoding and gating of cough.