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睡眠期间蓝斑去甲肾上腺素能传递的恢复

Restoration of locus coeruleus noradrenergic transmission during sleep.

作者信息

Sima Jiao, Zhang Yuchen, Farriday Declan, Ahn Andy Young-Eon, Lopez Eduardo Ramirez, Jin Chennan, Harrell Jade, Darmohray Dana, Silverman Daniel, Dan Yang

机构信息

Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.

出版信息

bioRxiv. 2024 Jul 5:2024.07.03.601820. doi: 10.1101/2024.07.03.601820.

DOI:10.1101/2024.07.03.601820
PMID:39005471
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11244971/
Abstract

Sleep is indispensable for health and wellbeing, but its basic function remains elusive. The locus coeruleus (LC) powerfully promotes arousal by releasing noradrenaline. We found that noradrenaline transmission is reduced by prolonged wakefulness and restored during sleep. Fiber-photometry imaging of noradrenaline using its biosensor showed that its release evoked by optogenetic LC neuron activation was strongly attenuated by three hours of sleep deprivation and restored during subsequent sleep. This is accompanied by the reduction and recovery of the wake-promoting effect of the LC neurons. The reduction of both LC evoked noradrenaline release and wake-inducing potency is activity dependent, and the rate of noradrenaline transmission recovery depends on mammalian target of rapamycin (mTOR) signaling. The decline and recovery of noradrenaline transmission also occur in spontaneous sleep-wake cycles on a timescale of minutes. Together, these results reveal an essential role of sleep in restoring transmission of a key arousal-promoting neuromodulator.

摘要

睡眠对健康和幸福至关重要，但其基本功能仍不清楚。蓝斑（LC）通过释放去甲肾上腺素有力地促进觉醒。我们发现，长时间清醒会减少去甲肾上腺素传递，而在睡眠期间会恢复。使用生物传感器对去甲肾上腺素进行纤维光度成像显示，光遗传学激活LC神经元所诱发的去甲肾上腺素释放，在睡眠剥夺三小时后会强烈减弱，并在随后的睡眠中恢复。这伴随着LC神经元促觉醒作用的减弱和恢复。LC诱发的去甲肾上腺素释放和促觉醒能力的降低均依赖于活动，而去甲肾上腺素传递恢复的速率取决于雷帕霉素靶蛋白（mTOR）信号传导。去甲肾上腺素传递的下降和恢复也会在以分钟为时间尺度的自发睡眠-觉醒周期中发生。这些结果共同揭示了睡眠在恢复一种关键促觉醒神经调节剂传递方面的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/cedb6bbacf8a/nihpp-2024.07.03.601820v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/5679d8930969/nihpp-2024.07.03.601820v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/ac2babc45179/nihpp-2024.07.03.601820v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/30901ab9cf91/nihpp-2024.07.03.601820v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/5b9dcd357822/nihpp-2024.07.03.601820v1-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/1751b47aa15e/nihpp-2024.07.03.601820v1-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/499b3c073ead/nihpp-2024.07.03.601820v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/aaee97a70b06/nihpp-2024.07.03.601820v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/92a88622abc7/nihpp-2024.07.03.601820v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/cedb6bbacf8a/nihpp-2024.07.03.601820v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/5679d8930969/nihpp-2024.07.03.601820v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/ac2babc45179/nihpp-2024.07.03.601820v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/30901ab9cf91/nihpp-2024.07.03.601820v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/5b9dcd357822/nihpp-2024.07.03.601820v1-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/1751b47aa15e/nihpp-2024.07.03.601820v1-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/499b3c073ead/nihpp-2024.07.03.601820v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/aaee97a70b06/nihpp-2024.07.03.601820v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/92a88622abc7/nihpp-2024.07.03.601820v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ef/11244971/cedb6bbacf8a/nihpp-2024.07.03.601820v1-f0004.jpg

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