The mammalian circadian pacemaker regulates wakefulness via CRF neurons in the paraventricular nucleus of the hypothalamus.

The mammalian circadian pacemaker regulates wakefulness via CRF neurons in the paraventricular nucleus of the hypothalamus.
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DOI:
10.1126/sciadv.abd0384
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发表时间:
2020-11
期刊:
影响因子:
13.6
通讯作者:
Yamanaka A
Yamanaka A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ono D;Mukai Y;Hung CJ;Chowdhury S;Sugiyama T;Yamanaka A

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A hypothalamic neuronal circuit mediates circadian-regulated wakefulness in mice. In mammals, the daily rhythms of physiological functions are timed by the central circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Although the importance of the SCN for the regulation of sleep/wakefulness has been suggested, little is known about the neuronal projections from the SCN, which regulate sleep/wakefulness. Here, we show that corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus mediate circadian rhythms in the SCN and regulate wakefulness. Optogenetic activation of CRF neurons promoted wakefulness through orexin/hypocretin neurons in the lateral hypothalamus. In vivo Ca2+ recording showed that CRF neurons were active at the initiation of wakefulness. Furthermore, chemogenetic suppression and ablation of CRF neurons decreased locomotor activity and time in wakefulness. Last, a combination of optical manipulation and Ca2+ imaging revealed that neuronal activity of CRF neurons was negatively regulated by GABAergic neurons in the SCN. Our findings provide notable insights into circadian regulation of sleep/wakefulness in mammals.
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