Introduction of respiratory pattern generators into models of respiratory control

We have adapted two models previously proposed as respiratory pattern generators (RPGs) into a neurochemical feed back control model of ventilation. The RPG models, non-dimensional as originally presented, consisted of oscillating circuits of either two or five interconnected neurons [Matsugu, M., Duffin, J., Poon, C.-S., 1998. Entrainment, instability, quasi-periodicity, and chaos in a compound neural oscillator. J. Comput. Neurosci. 5, 35-51; Botros, S.M., Bruce, E.N., 1990. Neural network implementation of a three-phase model of respiratory rhythm generation. Biol. Cybern. 63, 143-153]. The neurochemical model into which they were integrated [Longobardo, G., Evangelisti, C.J., Cherniack, N.S., 2002. Effects of neural drives on breathing in the awake state in humans. Respir. Physiol. 129, 317-333] included the effects of cerebral blood flow variation with CO2, vagal stretch receptors input and a multicompartment model of carbon dioxide stores. The methodology is described whereby these neuronal oscillator networks were quantified, a necessary step for their inclusion as RPGs in broader models of the overall control of respiration. Subsequent simulations of the ventilation response to carbon dioxide with either respiratory pattern generator model exhibited only a limited range in which tidal volume and frequency increased with increasing respiratory drive. With both models, frequency peaked and then declined, as did ventilation when PCO2 was greater than normal. The range of the models was extended if the respiratory pattern generators were considered to be composed of multiple neuronal oscillators or a single oscillator in which there was increasing phasic input that was gated or pacemaker driven.