Interdependence of cellular and network properties in respiratory rhythm generation.

How breathing is generated by the preBötzinger complex (preBötC) remains divided between two ideological frameworks, and a 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 "preinspiratory" spiking activity driven by feed-forward network interactions. Using computational modeling, we find that small 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 preinspiratory 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 preinspiratory spiking, are critical interdependent features of preBötC rhythmogenesis.