The use of multiscale systems biology approaches to facilitate understanding of complex control systems for airway protection

Abstract

Airway protection is a critically important function that prevents/limits the intrusion of foreign material into the pulmonary tree. A host of different behaviors participate in this process. The control, coordination, and execution of these behaviors is a complex process that has recently received increased attention. Data from human clinical and animal studies support the concept of a coordinated neural control system that governs the appropriate expression and sequencing of airway protective behaviors. Our current knowledge of the proposed neural control network for breathing, cough, swallow and other airway protective behaviors indicates that it is a highly complex system that can 'rewire' (reconfigure) itself to perform several different functions. Computational modeling and simulation have been used as tools to investigate this system. The results of modeling efforts have yielded motor output patterns of upper airway and respiratory muscles that are very similar to those recorded in vivo. Regulation and coordination of multiple different airway protective behaviors have been successfully simulated. Outcomes of simulation efforts support the hypothesis that computational modeling of airway protection can yield important testable hypotheses regarding brainstem neural network functions and organization. Modeling of complex systems can be challenging but the open availability of straight-forward computational tools is likely to result in increased implementation of modeling and simulation as adjuncts to traditional methods of investigation of the control of the upper airway.

Figure 1

Simpified core synaptic model for the medullary network producing breathing, cough, and swallow. The model is similar to that reported by Rybak and coworkers (Rybak et al. 2008) with several modifications to include elements related to the production of swallow. Populations of neurons are color coded based on major activities during the inspiratory phase, early expiratory phase (E1), and late expiratory phase (E2). colored half-circles show cooperative groups of inspiratory and expiratory neurons. The colored box shows motor outputs specifically related to the production of swallow. Current simulations include recently elucidated participation of modulatory circuits inferred from network connectivity data from the pontine respiratory group and medullary raphe nuclei.

Figure 2

Simulation of breathing and swallow. Traces represent moving averages of spinal and cranial motoneuron populations during simulated breathing and simulated swallow. Arrow indicates stimulation of simulated pharyngeal receptor afferent inputs to the system, as shown in Figure 1. Simulated swallow is depicted as a large burst in expiratory laryngeal (adductor) motoneurons, coincident with an increase in expiratory hypoglossal motoneuron discharge.