Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland.
Physiol Rev. 2020 Oct 1;100(4):1415-1454. doi: 10.1152/physrev.00027.2019. Epub 2020 Mar 12.
Animals synchronize to the environmental day-night cycle by means of an internal circadian clock in the brain. In mammals, this timekeeping mechanism is housed in the suprachiasmatic nucleus (SCN) of the hypothalamus and is entrained by light input from the retina. One output of the SCN is a neural code for circadian time, which arises from the collective activity of neurons within the SCN circuit and comprises two fundamental components: ) periodic alterations in the spontaneous excitability of individual neurons that result in higher firing rates during the day and lower firing rates at night, and ) synchronization of these cellular oscillations throughout the SCN. In this review, we summarize current evidence for the identity of ion channels in SCN neurons and the mechanisms by which they set the rhythmic parameters of the time code. During the day, voltage-dependent and independent Na and Ca currents, as well as several K currents, contribute to increased membrane excitability and therefore higher firing frequency. At night, an increase in different K currents, including Ca-activated BK currents, contribute to membrane hyperpolarization and decreased firing. Layered on top of these intrinsically regulated changes in membrane excitability, more than a dozen neuromodulators influence action potential activity and rhythmicity in SCN neurons, facilitating both synchronization and plasticity of the neural code.
动物通过大脑中的内部生物钟来同步环境的日夜周期。在哺乳动物中，这种计时机制位于下丘脑的视交叉上核（SCN）中，并通过视网膜的光输入进行同步。SCN 的一个输出是生物钟的神经编码，它源于 SCN 电路中神经元的集体活动，包括两个基本组成部分：) 单个神经元自发性兴奋性的周期性改变，导致白天的发射率更高，夜间的发射率更低，以及) SCN 中这些细胞振荡的同步。在这篇综述中，我们总结了 SCN 神经元中离子通道的身份以及它们设置时间码节律参数的机制的当前证据。在白天，电压依赖性和非依赖性 Na 和 Ca 电流以及几种 K 电流有助于增加膜兴奋性，从而提高发射频率。在夜间，包括 Ca 激活的 BK 电流在内的多种不同 K 电流的增加有助于膜超极化和降低发射率。在这些内在调节的膜兴奋性变化之上，十几种神经调质影响 SCN 神经元的动作电位活动和节律性，促进神经编码的同步和可塑性。
