Robustness of respiratory rhythm generation across dynamic regimes

Abstract

A central issue in the study of the neural generation of respiratory rhythms is the role of the intrinsic pacemaking capabilities that some respiratory neurons exhibit. The debate on this issue has occurred in parallel to investigations of interactions among respiratory network neurons and how these contribute to respiratory behavior. In this computational study, we demonstrate how these two issues are inextricably linked. We use simulations and dynamical systems analysis to show that once a conditional respiratory pacemaker, which can be tuned across oscillatory and non-oscillatory dynamic regimes in isolation, is embedded into a respiratory network, its dynamics become masked: the network exhibits similar dynamic properties regardless of the conditional pacemaker nodes tuning, and that nodes outputs are dominated by network influences. Furthermore, the outputs of the respiratory central pattern generator as a whole are invariant to these changes of dynamical properties, which ensures flexible and robust performance over a wide dynamic range. Author summaryBreathing movements in mammals are generated by brainstem respiratory central pattern generator (CPG) networks, which incorporate an excitatory oscillator located in the pre-Botzinger Complex (preBotC) that can exhibit autorhythmic behavior. To understand how these autorhythmic properties impact CPG network dynamical performance, we performed computational studies with an established modeling framework to systematically analyze network behavior when the preBotC excitatory neurons intrinsic dynamics are tuned to operate in autorhythmic versus non-autorhythmic regimes. Both of these regimes enable rhythmic activity of the CPG network, and we show that the rhythm and its responses to various manipulations are preserved across the tunings of intrinsic properties of the preBotC component. Correspondingly, the emergence of behaviorally appropriate rhythmic patterns of network activity is maintained across preBotC regimes, accompanied by an expansion of the ranges of network output frequencies and amplitudes beyond those attainable with either preBotC regime alone. These results lead to the novel conclusion and concept that the dynamical operation of the CPG is functionally highly robust with respect to the rhythmogenic state of the preBotC excitatory circuits, which could represent a key property for preserved respiratory function across varying conditions and demands on network performance.