Chevalier Marc, Toporikova Natalia, Simmers John, Thoby-Brisson Muriel
Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS UMR 5287, Université de Bordeaux, Bordeaux, France.
Department of Biology, Washington and Lee University, Lexington, United States.
Elife. 2016 Jul 19;5:e16125. doi: 10.7554/eLife.16125.
Breathing is a vital rhythmic behavior generated by hindbrain neuronal circuitry, including the preBötzinger complex network (preBötC) that controls inspiration. The emergence of preBötC network activity during prenatal development has been described, but little is known regarding inspiratory neurons expressing pacemaker properties at embryonic stages. Here, we combined calcium imaging and electrophysiological recordings in mouse embryo brainstem slices together with computational modeling to reveal the existence of heterogeneous pacemaker oscillatory properties relying on distinct combinations of burst-generating INaP and ICAN conductances. The respective proportion of the different inspiratory pacemaker subtypes changes during prenatal development. Concomitantly, network rhythmogenesis switches from a purely INaP/ICAN-dependent mechanism at E16.5 to a combined pacemaker/network-driven process at E18.5. Our results provide the first description of pacemaker bursting properties in embryonic preBötC neurons and indicate that network rhythmogenesis undergoes important changes during prenatal development through alterations in both circuit properties and the biophysical characteristics of pacemaker neurons.
呼吸是一种由后脑神经回路产生的重要节律性行为，其中包括控制吸气的前包钦格复合体网络（preBötC）。产前发育过程中preBötC网络活动的出现已有描述，但对于胚胎阶段表达起搏器特性的吸气神经元却知之甚少。在这里，我们将小鼠胚胎脑干切片中的钙成像和电生理记录与计算建模相结合，以揭示依赖于爆发性产生的INaP和ICAN电导的不同组合的异质性起搏器振荡特性的存在。不同吸气起搏器亚型的各自比例在产前发育过程中发生变化。与此同时，网络节律发生从E16.5时纯粹依赖INaP/ICAN的机制转变为E18.5时起搏器/网络驱动的联合过程。我们的结果首次描述了胚胎preBötC神经元中的起搏器爆发特性，并表明网络节律发生在产前发育过程中通过回路特性和起搏器神经元生物物理特性的改变而经历了重要变化。
