The hypothalamic link between arousal and sleep homeostasis in mice.
The hypothalamic link between arousal and sleep homeostasis in mice.
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DOI：
10.1073/pnas.2101580118
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发表时间：
2021-12-21
影响因子：
11.1
通讯作者：
Vyazovskiy VV
中科院分区：
文献类型：
--
作者：
Yamagata T;Kahn MC;Prius-Mengual J;Meijer E;Šabanović M;Guillaumin MCC;van der Vinne V;Huang YG;McKillop LE;Jagannath A;Peirson SN;Mann EO;Foster RG;Vyazovskiy VV
我们目前对睡眠如何调节的理解是基于睡眠稳态模型，该模型定义了一个称为过程S的变量作为睡眠需求的度量，以及所谓的状态转换“触发器”模型，该模型建立在皮层下促进睡眠和促进唤醒电路之间相互拮抗关系的概念上。睡眠开关和S过程之间相互作用的神经生物学基础是未知的。我们的研究确定了下丘脑回路在调节状态内大脑活动或唤醒水平方面的一个先前未被认识的作用，这反过来又决定了睡眠的稳态驱动。睡眠和觉醒并不是简单的、同质的全有或全无状态，而是代表了一系列亚状态，其特征在于局部和整体层面的行为、觉醒水平以及大脑活动。到目前为止，下丘脑回路在睡眠-觉醒控制中的作用主要是研究其对快速状态转换的贡献。相反，下丘脑是否调节状态内动力学（状态“质量”）及其功能意义仍然未被探索。在这里，我们表明，光激活的抑制性神经元的外侧视前区（LPO）的成年男性和女性实验室小鼠的下丘脑不仅触发觉醒从睡眠中，但由此产生的清醒状态也具有激活的脑电图（EEG）模式，这表明唤醒水平的增加。这与睡眠压力的更快积累有关，反映在随后的睡眠期间更高的EEG慢波活动（SWA）中。与此相反，抑制性LPO神经元的光抑制并没有导致警觉状态的变化，但与自发睡眠期间持续增加的EEG SWA相关。这些研究结果表明，LPO在调节唤醒水平中的作用，我们建议将其作为塑造睡眠-觉醒状态日常结构的关键变量。
Our current understanding of how sleep is regulated is based upon the model of sleep homeostasis, which defines a variable called Process S as a measure of sleep need, and a so-called “flip-flop” model of state switching, which builds on a notion of a mutually antagonistic relationship between subcortical sleep-promoting and wake-promoting circuits. The neurobiological substrates of the interaction between the sleep switch and Process S are unknown. Our study identifies a previously unrecognized role of hypothalamic circuitry in tuning within-state brain activity or levels of arousal, which in turn determine the homeostatic drive for sleep. Sleep and wakefulness are not simple, homogenous all-or-none states but represent a spectrum of substates, distinguished by behavior, levels of arousal, and brain activity at the local and global levels. Until now, the role of the hypothalamic circuitry in sleep–wake control was studied primarily with respect to its contribution to rapid state transitions. In contrast, whether the hypothalamus modulates within-state dynamics (state “quality”) and the functional significance thereof remains unexplored. Here, we show that photoactivation of inhibitory neurons in the lateral preoptic area (LPO) of the hypothalamus of adult male and female laboratory mice does not merely trigger awakening from sleep, but the resulting awake state is also characterized by an activated electroencephalogram (EEG) pattern, suggesting increased levels of arousal. This was associated with a faster build-up of sleep pressure, as reflected in higher EEG slow-wave activity (SWA) during subsequent sleep. In contrast, photoinhibition of inhibitory LPO neurons did not result in changes in vigilance states but was associated with persistently increased EEG SWA during spontaneous sleep. These findings suggest a role of the LPO in regulating arousal levels, which we propose as a key variable shaping the daily architecture of sleep–wake states.
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影响因子：
16.6
作者：
Bartram J;Kahn MC;Tuohy S;Paulsen O;Wilson T;Mann EO
通讯作者：
Mann EO
影响因子：
16.6
作者：
Fisher, Simon P.;Cui, Nanyi;McKillop, Laura E.;Gemignani, Jessica;Bannerman, David M.;Oliver, Peter L.;Peirson, Stuart N.;Vyazovskiy, Vladyslav V.
通讯作者：
Vyazovskiy, Vladyslav V.
视觉皮层回路中兴奋-抑制平衡的每日振荡
影响因子：
16.2
作者：
Bridi, Michelle C. D.;Zong, Fang-Jiao;Min, Xia;Luo, Nancy;Tran, Trinh;Qiu, Jiaqian;Severin, Daniel;Zhang, Xue-Ting;Wang, Guanglin;Zhu, Zheng-Jiang;He, Kai-Wen;Kirkwood, Alfredo
通讯作者：
Kirkwood, Alfredo
影响因子：
56.9
作者：
Bruening, Franziska;Noya, Sara B.;Robles, Maria S.
通讯作者：
Robles, Maria S.
影响因子：
25
作者：
Gent TC;Bandarabadi M;Herrera CG;Adamantidis AR
通讯作者：
Adamantidis AR