Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101.
Pulmonary, Critical Care and Sleep Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195.
Proc Natl Acad Sci U S A. 2024 May 7;121(19):e2318757121. doi: 10.1073/pnas.2318757121. Epub 2024 May 1.
How breathing is generated by the preBötzinger complex (preBötC) remains divided between two ideological frameworks, and a persistent sodium current (I) lies at the heart of this debate. Although I 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 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 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. Our results support a unifying hypothesis where I and excitatory network interactions, but not intrinsic bursting or preinspiratory spiking, are critical interdependent features of preBötC rhythmogenesis.
呼吸如何由 PreBötzinger 复合体（preBötC）产生，在两个思想框架之间存在分歧，而持续的钠离子电流（I）是这场争论的核心。尽管 I 广泛表达，但起搏器假说认为它是必不可少的，因为它赋予一小部分神经元内在的爆发或“起搏器”活动。相比之下，爆发理论认为 I 是可有可无的，因为节律是由前吸气期的尖峰活动驱动的，这种尖峰活动是由前馈网络相互作用产生的。通过计算建模，我们发现尖峰形状的微小变化可以将 I 与内在爆发分离。与许多实验基准一致，在模拟氧合、发育、细胞外钾和温度变化过程中，对尖峰形状的条件作用改变了内在爆发和前吸气期尖峰活动的出现，而不改变 I 的作用。我们的结果支持一个统一的假说，即 I 和兴奋性网络相互作用，而不是内在爆发或前吸气期尖峰活动，是 preBötC 节律产生的关键相互依赖特征。
