Modeling neural mechanisms for genesis of respiratory rhythm and pattern. III. Comparison of model performances during afferent nerve stimulation.

The goal of the present study was to evaluate the relative plausibility of the models of the central respiratory pattern generator (CRPG) proposed in our previous paper. To test the models, we compared changes in generated patterns with the experimentally observed alterations of the respiratory pattern induced by various stimuli applied to superior laryngeal (SLN), vagus and carotid sinus (CS) nerves. In all models, short-duration SLN simulation caused phase-resetting behavior consistent with experimental data. Relatively weak sustained SLN stimulation elicited a two-phase rhythm comprising inspiration and postinspiration whereas a stronger stimulation stopped oscillations in the postinspiratory phase ("postinspiratory apnea"). In all models, sustained vagus nerve stimulation produced postinspiratory apnea. A short vagal stimulus delivered during inspiration terminated this phase. The threshold for inspiratory termination decreased during the course of the inspiratory phase. The effects of short-duration vagal stimulation applied during expiration were different in different models. In model 1, stimuli delivered in the postinspiratory phase prolonged expiration whereas the late expiratory phase was insensitive to vagal stimulation. No insensitive period was found in model 2 because vagal stimuli delivered at any time during expiration prolonged this phase. Model 3 demonstrated a short period insensitive to vagal stimulation at the very end of expiration. When phasic CS nerve stimulation was applied during inspiration or the first half of expiration, the performances of all models were similar and consistent with experimental data: stimuli delivered at the beginning inspiration shortened this phase whereas stimuli applied in the middle or at the end of inspiration prolonged it and stimuli delivered in the first half of expiration prolonged the expiratory interval. Behavior of the models were different when CS stimuli were delivered during the late expiratory phase. In model 1, these stimuli were ineffective or shortened expiration initiating the next inspiration. Alternatively, in models 2 and 3, they caused a prolongation of expiration. Although all CRPG models demonstrated a number of plausible alterations in the respiratory pattern elicited by afferent nerve stimulation, the behavior of model 1 was most consistent with experimental data. Taking into account differences in the model architectures and employed neural mechanisms, we suggest that the concept of respiratory rhythmogenesis based on the essential role of postinspiratory neurons is more plausible than the concept employing specific functional properties of decrementing expiratory (dec-E) neurons and that the ramp firing pattern of the late expiratory neuron is more likely to reflect intrinsic properties than disinhibition from the dec-E neurons.