A model for control of breathing in mammals: coupling neural dynamics to peripheral gas exchange and transport.

A new model for aspects of the control of respiration in mammals has been developed. The model integrates a reduced representation of the brainstem respiratory neural controller together with peripheral gas exchange and transport mechanisms. The neural controller consists of two components. One component represents the inspiratory oscillator in the pre-Bötzinger complex (pre-BötC) incorporating biophysical mechanisms for rhythm generation. The other component represents the ventral respiratory group (VRG), which is driven by the pre-BötC for generation of inspiratory (pre)motor output. The neural model was coupled to simplified models of the lungs incorporating oxygen and carbon dioxide transport. The simplified representation of the brainstem neural circuitry has regulation of both frequency and amplitude of respiration and is done in response to partial pressures of oxygen and carbon dioxide in the blood using proportional (P) and proportional plus integral (PI) controllers. We have studied the coupled system under open and closed loop control. We show that two breathing regimes can exist in the model. In one regime an increase in the inspiratory frequency is accompanied by an increase in amplitude. In the second regime an increase in frequency is accompanied by a decrease in amplitude. The dynamic response of the model to changes in the concentration of inspired O2 or inspired CO2 was compared qualitatively with experimental data reported in the physiological literature. We show that the dynamic response with a PI-controller fits the experimental data better but suggests that when high levels of CO2 are inspired the respiratory system cannot reach steady state. Our model also predicts that there could be two possible mechanisms for apnea appearance when 100% O2 is inspired following a period of 5% inspired O2. This paper represents a novel attempt to link neural control and gas transport mechanisms, highlights important issues in amplitude and frequency control and sets the stage for more complete neurophysiological control models.