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

Abstract:

: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.

journal_name

Sci Adv

journal_title

Science advances

authors

Ono D,Mukai Y,Hung CJ,Chowdhury S,Sugiyama T,Yamanaka A

doi

10.1126/sciadv.abd0384

subject

Has Abstract

pub_date

2020-11-06 00:00:00

issue

45

issn

2375-2548

pii

6/45/eabd0384

journal_volume

6

pub_type

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