Generation of the respiratory rhythm: modelling the inspiratory off switch as a neural integrator

Abstract

Neural integration is involved in the respiratory central processing of vagal afferent activity originating from lung mechanoreceptors. In the present work it is assumed that not only vagal activity, but also the incoming activities of the other inputs which converge into the “inspiratory off-switch”, are processed there by integration. Moreover, integration is considered to be essential for the inspiratory off-switch function. This assumption leads to a novel mathematical model, in which constancy of the inspiratory off-switch threshold and absence of a central inspiratory activity input to the inspiratory off-switch are postulated. The model accurately predicts the relationship between timing and depth of breathing measured experimentally under several steady-state conditions, including peripheral and central chemoreceptor stimulation, increased body temperature, increased elastic and flow resistive loads, and bilateral vagotomy. The model also provides adequate simulation of the integrative vagal processing and questions the idea that “accommodative” vagal processing originates from a separate process different to integration at the inspiratory off-switch. The assumption that integration is essential for the inspiratory off-switching suggests a simple basis for interpreting, electrophysiological properties of bulbo-pontine inspiratory neurons in terms of a neuronal circuit that acts like an integrator. The prediction of a new type of inspiratory neuron is discussed.