Interdependence of cellular and network properties in respiratory rhythm generation

Proc Natl Acad Sci U S A. 2024 May 7;121(19):e2318757121. doi: 10.1073/pnas.2318757121. Epub 2024 May 1.

Abstract

How breathing is generated by the preBötzinger complex (preBötC) remains divided between two ideological frameworks, and a persistent sodium current (INaP) lies at the heart of this debate. Although INaP 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 INaP 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 INaP 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 INaP. Our results support a unifying hypothesis where INaP and excitatory network interactions, but not intrinsic bursting or preinspiratory spiking, are critical interdependent features of preBötC rhythmogenesis.

Keywords: afterhyperpolarization; central pattern generation; respiratory control; rhythm generation; spike shape.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials* / physiology
  • Animals
  • Computer Simulation
  • Models, Neurological
  • Nerve Net / physiology
  • Neurons / physiology
  • Respiration
  • Respiratory Center / physiology
  • Sodium / metabolism

Substances

  • Sodium