Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States.
Department of Physics, University of New Hampshire, Durham, United States.
Elife. 2019 Mar 25;8:e41555. doi: 10.7554/eLife.41555.
An autorhythmic population of excitatory neurons in the brainstem pre-Bötzinger complex is a critical component of the mammalian respiratory oscillator. Two intrinsic neuronal biophysical mechanisms-a persistent sodium current ([Formula: see text]) and a calcium-activated non-selective cationic current ([Formula: see text])-were proposed to individually or in combination generate cellular- and circuit-level oscillations, but their roles are debated without resolution. We re-examined these roles in a model of a synaptically connected population of excitatory neurons with [Formula: see text] and [Formula: see text]. This model robustly reproduces experimental data showing that rhythm generation can be independent of [Formula: see text] activation, which determines population activity amplitude. This occurs when [Formula: see text] is primarily activated by neuronal calcium fluxes driven by synaptic mechanisms. Rhythm depends critically on [Formula: see text] in a subpopulation forming the rhythmogenic kernel. The model explains how the rhythm and amplitude of respiratory oscillations involve distinct biophysical mechanisms.
脑桥 Pre-Bötzinger 复合体中的自主兴奋神经元群体是哺乳动物呼吸振荡器的关键组成部分。两种内在的神经元生物物理机制——持续钠电流([Formula: see text])和钙激活非选择性阳离子电流([Formula: see text])——被提出单独或组合产生细胞和电路水平的振荡,但它们的作用仍存在争议,尚未得到解决。我们在一个具有[Formula: see text]和[Formula: see text]的突触连接兴奋神经元群体模型中重新研究了这些作用。该模型很好地再现了实验数据,表明节律产生可以独立于[Formula: see text]的激活,而[Formula: see text]决定了群体活动的幅度。当[Formula: see text]主要由突触机制驱动的神经元钙通量激活时,就会发生这种情况。节律的产生严重依赖于形成节律核的亚群中的[Formula: see text]。该模型解释了呼吸振荡的节律和幅度如何涉及不同的生物物理机制。