Interdependence of cellular and network properties in respiratory rhythmogenesis.
Interdependence of cellular and network properties in respiratory rhythmogenesis.
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呼吸节律发生中细胞和网络特性的相互依赖性。
DOI：
10.1101/2023.10.30.564834
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Baertsch,NathanA
中科院分区：
文献类型：
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作者：
Phillips,RyanS;Baertsch,NathanA
前伯青格复合体（preBötC）如何产生呼吸仍然存在两种意识形态框架，持续钠电流（INaP）是这场辩论的核心。虽然INaP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固有的爆发或“起搏器”活动。相比之下，爆发波理论认为INaP节律是由前馈网络相互作用驱动的“吸气前”尖峰活动产生的。使用计算模型，我们发现，尖峰形状的变化可以解离INaP从内在爆发。与许多实验基准一致，在氧合、发育、细胞外钾和温度的模拟变化期间对峰形的条件性影响改变了内在爆发和吸气前峰的患病率，而不改变INaP的作用。我们的研究结果支持一个统一的假设，INaP和兴奋性网络的相互作用，但不是内在的爆发或吸气前尖峰，是重要的相互依赖的特点preBötC节律。
How breathing is generated by the preBötzinger Complex (preBötC) remains divided between two ideological frameworks, and the 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 “pre-inspiratory” spiking activity driven by feed-forward network interactions. Using computational modeling, we discover that 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 pre-inspiratory spiking without altering the role of INaP. Our results support a unifying hypothesis where INaP and excitatory network interactions, but not intrinsic bursting or pre-inspiratory spiking, are critical interdependent features of preBötC rhythmogenesis.