Phase- and state-dependent modulation of breathing pattern by preBötzinger complex somatostatin expressing neurons.
Phase- and state-dependent modulation of breathing pattern by preBötzinger complex somatostatin expressing neurons.
复制标题
preBötzinger复杂生长抑素表达神经元对呼吸模式的相位和状态依赖性调节。
DOI：
10.1113/jp282002
复制
发表时间：
2022-01
影响因子：
5.5
通讯作者：
Feldman, Jack L.
中科院分区：
文献类型：
--
作者：
Abreu, Raquel P. Sousa;Bondarenko, Evgeny;Feldman, Jack L.
随着神经元亚型的分类越来越多，描述其功能作用至关重要。表达神经肽生长抑素（SST）的preBötC亚群被分类为主要兴奋性、吸气调节性和非节律性。我们进一步表征了它们的表型同一性; 87%为谷氨酸能，其余为甘氨酸能和/或GABA能。然后，我们使用光遗传学来研究它们在麻醉和自由活动小鼠中的调节作用。在麻醉小鼠中，对preBötC SST+神经元的短光刺激（100 ms）以相态和状态依赖的方式调节呼吸相关变量;在较高（≥2.5 Hz）与较低（<2.5 Hz）呼吸频率下，吸气持续时间、吸气峰值幅度（Emax）和相态的变化不同。此外，我们观察到呼气期间光刺激的双相效应是概率性的，即，在连续周期中以相同相位给予的光刺激可以引起相反的反应（相位的延长与缩短）。这些意想不到的概率状态和相位依赖性的光刺激反应暴露的preBötC的属性，没有预测，不能很容易地占在当前模型的preBötC模式生成。在自由活动的小鼠中，长时间的光刺激降低了常氧、低氧或高碳酸血症下的f，并增加了f，产生了相位提前，这与f≥2.5 Hz时麻醉小鼠的结果相似。我们得出结论，preBötC SST+神经元是一个关键的调解人的非凡和必要的不稳定性的呼吸模式。
As neuronal subtypes are increasingly categorized, delineating their functional role is paramount. The preBötzinger Complex (preBötC) subpopulation expressing the neuropeptide somatostatin (SST) is classified as mostly excitatory, inspiratory-modulated and not rhythmogenic. We further characterized their phenotypic identity; 87% were glutamatergic and the balance were glycinergic and/or GABAergic. We then used optogenetics to investigate their modulatory role in both anesthetized and freely moving mice. In anesthetized mice, short photostimulation (100 ms) of preBötC SST+ neurons modulated breathing-related variables in a combinatory phase- and state-dependent manner; changes in inspiratory duration, inspiratory peak amplitude (Amp), and phase were different at higher (≥2.5 Hz) vs. lower (<2.5 Hz) breathing frequency. Moreover, we observed a biphasic effect of photostimulation during expiration that is probabilistic, i.e., photostimulation given at the same phase in consecutive cycles can evoke opposite responses (lengthening vs. shortening of the phase). These unexpected probabilistic state- and phase-dependent responses to photostimulation exposed properties of the preBötC that were not predicted and cannot be readily accounted for in current models of preBötC pattern generation. In freely moving mice, prolonged photostimulation decreased f in normoxia, hypoxia, or hypercapnia, and increased Amp and produced a phase advance, which was similar to the results in anesthetized mice when f≥2.5 Hz. We conclude that preBötC SST+ neurons are a key mediator of the extraordinary and essential lability of breathing pattern.