Interdependence of cellular and network properties in respiratory rhythmogenesis

How breathing is generated by the preBötzinger Complex (preBötC) remains divided between two ideological frameworks, and the persistent sodium current (I(NaP)) lies at the heart of this debate. Although I(NaP) is widely expressed, the pacemaker hypothesis considers it essential because it endows a small subset of neurons with intrinsic bursting or “pacemaker” activity. In contrast, burstlet theory considers I(NaP) dispensable because rhythm emerges from “pre-inspiratory” spiking activity driven by feed-forward network interactions. Using computational modeling, we discover that changes in spike shape can dissociate I(NaP) from intrinsic bursting. Consistent with many experimental benchmarks, conditional effects on spike shape during simulated changes in oxygenation, development, extracellular potassium, and temperature alter the prevalence of intrinsic bursting and pre-inspiratory spiking without altering the role of I(NaP). Our results support a unifying hypothesis where I(NaP) and excitatory network interactions, but not intrinsic bursting or pre-inspiratory spiking, are critical interdependent features of preBötC rhythmogenesis.