Allen Charles N, Nitabach Michael N, Colwell Christopher S
Oregon Institute of Occupational Health Sciences and Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon 97239.
Department of Cellular and Molecular Physiology and Department of Genetics, Yale School of Medicine, New Haven, Connecticut 06520.
Cold Spring Harb Perspect Biol. 2017 May 1;9(5):a027714. doi: 10.1101/cshperspect.a027714.
Neuronal circadian oscillators in the mammalian and brain express a circadian clock comprised of interlocking gene transcription feedback loops. The genetic clock regulates the membrane electrical activity by poorly understood signaling pathways to generate a circadian pattern of action potential firing. During the day, Na channels contribute an excitatory drive for the spontaneous activity of circadian clock neurons. Multiple types of K channels regulate the action potential firing pattern and the nightly reduction in neuronal activity. The membrane electrical activity possibly signaling by changes in intracellular Ca and cyclic adenosine monophosphate (cAMP) regulates the activity of the gene clock. A decline in the signaling pathways that link the gene clock and neural activity during aging and disease may weaken the circadian output and generate significant impacts on human health.
哺乳动物大脑中的神经元昼夜节律振荡器表达一种由相互连锁的基因转录反馈环组成的昼夜节律时钟。基因时钟通过鲜为人知的信号通路调节膜电活动，以产生动作电位发放的昼夜节律模式。在白天，钠通道为昼夜节律时钟神经元的自发活动提供兴奋性驱动。多种类型的钾通道调节动作电位发放模式以及夜间神经元活动的减少。膜电活动可能通过细胞内钙和环磷酸腺苷（cAMP）的变化进行信号传递，从而调节基因时钟的活动。衰老和疾病期间连接基因时钟与神经活动的信号通路的衰退可能会削弱昼夜节律输出，并对人类健康产生重大影响。
