Circadian VIPergic Neurons of the Suprachiasmatic Nuclei Sculpt the Sleep-Wake Cycle.

Circadian VIPergic Neurons of the Suprachiasmatic Nuclei Sculpt the Sleep-Wake Cycle.
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DOI:
10.1016/j.neuron.2020.08.001
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发表时间:
2020-11-11
期刊:
影响因子:
16.2
通讯作者:
Brown SA
Brown SA
中科院分区:
医学1区
文献类型:
--
作者:
Collins B;Pierre-Ferrer S;Muheim C;Lukacsovich D;Cai Y;Spinnler A;Herrera CG;Wen S;Winterer J;Belle MDC;Piggins HD;Hastings M;Loudon A;Yan J;Földy C;Adamantidis A;Brown SA

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虽然哺乳动物的休息-活动周期是由下丘脑视交叉上核(SCN)中的“主时钟”控制的,但尚不清楚单个SCN神经元的放电如何控制日常活动的个体特征。在这里,我们证明了一个特定的转录组识别的小鼠VIP+ SCN神经元的人口是活跃的“错误”的时间白天-夜间-当大多数SCN神经元是沉默的。使用化学遗传学和光遗传学策略,我们发现这些神经元及其细胞时钟对于夜间睡眠的门控和计时是必要和足够的,但对白天睡眠没有影响。我们认为,老鼠的夜间睡眠,类似于人类的午睡,是一种“硬连线”的属性,由主时钟的特定神经元门控,有利于随后的警觉性在黎明前(昼夜节律的“清醒维持区”)。因此,SCN不仅仅是一个24小时节拍器:特定人群塑造了睡眠-觉醒周期的关键特征。SCN的特定VIP+神经元在夜间放电,而大多数其他神经元都沉默。激活或沉默这些VIP+神经元控制夜间睡眠,但不控制白天睡眠。这些特定神经元内的昼夜节律时钟对每天的“午睡”进行计时。这些神经元的活动反过来又编程了随后的一天结束时的警觉性。“主”昼夜节律钟通常通过紧张的白天放电来指示白天和黑夜。当SCN的其余部分沉默时,一群特定的神经元活跃,指导夜间的“午睡”睡眠,而不是白天的睡眠,从而计时一天结束时的警觉性。
Although the mammalian rest-activity cycle is controlled by a “master clock” in the suprachiasmatic nucleus (SCN) of the hypothalamus, it is unclear how firing of individual SCN neurons gates individual features of daily activity. Here, we demonstrate that a specific transcriptomically identified population of mouse VIP+ SCN neurons is active at the “wrong” time of day—nighttime—when most SCN neurons are silent. Using chemogenetic and optogenetic strategies, we show that these neurons and their cellular clocks are necessary and sufficient to gate and time nighttime sleep but have no effect upon daytime sleep. We propose that mouse nighttime sleep, analogous to the human siesta, is a “hard-wired” property gated by specific neurons of the master clock to favor subsequent alertness prior to dawn (a circadian “wake maintenance zone”). Thus, the SCN is not simply a 24-h metronome: specific populations sculpt critical features of the sleep-wake cycle. Specific VIP+ neurons of the SCN fire at night when most others are silent Activating or silencing these VIP+ neurons controls nighttime but not daytime sleep Circadian clockwork within these specific neurons times the daily “siesta” The activity of these neurons, in turn, programs subsequent end-of-day alertness The “master” circadian clock generally indicates day and night by tonic daytime firing. A specific population of neurons, active when the rest of the SCN is silent, directs nighttime “siesta” sleep but not daytime sleep, thereby timing end-of-day alertness.
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