Center for Integrative Brain Research, Seattle Children's Research Institute, 1900 9th Avenue JMB10, Seattle, WA, 98101, USA.
Department of Neurological Surgery, University of Washington, 1900 9th Avenue, JMB10, Seattle, WA, 98101, USA.
Nat Commun. 2018 Feb 26;9(1):843. doi: 10.1038/s41467-018-03223-x.
The preBötzinger Complex (preBötC), a medullary network critical for breathing, relies on excitatory interneurons to generate the inspiratory rhythm. Yet, half of preBötC neurons are inhibitory, and the role of inhibition in rhythmogenesis remains controversial. Using optogenetics and electrophysiology in vitro and in vivo, we demonstrate that the intrinsic excitability of excitatory neurons is reduced following large depolarizing inspiratory bursts. This refractory period limits the preBötC to very slow breathing frequencies. Inhibition integrated within the network is required to prevent overexcitation of preBötC neurons, thereby regulating the refractory period and allowing rapid breathing. In vivo, sensory feedback inhibition also regulates the refractory period, and in slowly breathing mice with sensory feedback removed, activity of inhibitory, but not excitatory, neurons restores breathing to physiological frequencies. We conclude that excitation and inhibition are interdependent for the breathing rhythm, because inhibition permits physiological preBötC bursting by controlling refractory properties of excitatory neurons.
预前包钦格复合体（preBötC）是一种对呼吸至关重要的延髓网络，依赖兴奋性中间神经元产生吸气节律。然而，preBötC 的一半神经元是抑制性的，抑制在节律产生中的作用仍存在争议。我们使用在体和离体的光遗传学和电生理学方法证明，在大的去极化吸气爆发后，兴奋性神经元的内在兴奋性降低。这个不应期限制了 preBötC 只能产生非常慢的呼吸频率。网络内整合的抑制作用是必需的，以防止 preBötC 神经元的过度兴奋，从而调节不应期并允许快速呼吸。在体内，感觉反馈抑制也调节不应期，在去除感觉反馈的缓慢呼吸的小鼠中，抑制性神经元的活动而不是兴奋性神经元的活动将呼吸恢复到生理频率。我们得出结论，兴奋和抑制对于呼吸节律是相互依存的，因为抑制通过控制兴奋性神经元的不应性来允许生理 preBötC 爆发。
