Feed-forward and reciprocal inhibition for gain and phase timing control in a computational model of repetitive cough

We investigated the hypothesis, motivated in part by a coordinated computational cough network model, that second-order neurons in the nucleus tractus solitarius (NTS) act as a filter and shape afferent input to the respiratory network during the production of cough. In vivo experiments were conducted on anesthetized spontaneously breathing cats. Cough was elicited by mechanical stimulation of the intrathoracic airways. Electromyograms of the parasternal (inspiratory) and rectus abdominis (expiratory) muscles and esophageal pressure were recorded. In vivo data revealed that expiratory motor drive during bouts of repetitive coughs is variable: peak expulsive amplitude increases from the first cough, peaks about the eighth or ninth cough, and then decreases through the remainder of the bout. Model simulations indicated that feed-forward inhibition of a single second-order neuron population is not sufficient to account for this dynamic feature of a repetitive cough bout. When a single second-order population was split into two subpopulations (inspiratory and expiratory), the resultant model produced simulated expiratory motor bursts that were comparable to in vivo data. However, expiratory phase durations during these simulations of repetitive coughing had less variance than those in vivo. Simulations in which reciprocal inhibitory processes between inspiratory-decrementing and expiratory-augmenting-late neurons were introduced exhibited increased variance in the expiratory phase durations. These results support the prediction that serial and parallel processing of airway afferent signals in the NTS play a role in generation of the motor pattern for cough.