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蓝斑去甲肾上腺素活动介导睡眠中的感觉诱发觉醒。

Locus coeruleus norepinephrine activity mediates sensory-evoked awakenings from sleep.

机构信息

Department Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.

出版信息

Sci Adv. 2020 Apr 8;6(15):eaaz4232. doi: 10.1126/sciadv.aaz4232. eCollection 2020 Apr.

DOI:10.1126/sciadv.aaz4232
PMID:32285002
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7141817/
Abstract

A defining feature of sleep is reduced responsiveness to external stimuli, but the mechanisms mediating sensory-evoked arousal remain unclear. We hypothesized that reduced locus coeruleus (LC) norepinephrine (NE) activity during sleep mediates unresponsiveness, and its action promotes sensory-evoked awakenings. We tested this using electrophysiological, behavioral, pharmacological, and optogenetic techniques alongside auditory stimulation in freely behaving rats. We found that systemic reduction in NE signaling lowered probability of sound-evoked awakenings (SEAs). The level of tonic LC activity during sleep anticipated SEAs. Optogenetic LC activation promoted arousal as evident in sleep-wake transitions, EEG desynchronization, and pupil dilation. Minimal LC excitation before sound presentation increased SEA probability. Optogenetic LC silencing using a soma-targeted anion-conducting channelrhodopsin (stGtACR2) suppressed LC spiking and constricted pupils. Brief periods of LC opto-silencing reduced the probability of SEAs. Thus, LC-NE activity determines the likelihood of sensory-evoked awakenings, and its reduction during sleep constitutes a key factor mediating behavioral unresponsiveness.

摘要

睡眠的一个显著特征是对外界刺激的反应能力降低，但介导感觉诱发觉醒的机制仍不清楚。我们假设，睡眠期间蓝斑核（LC）去甲肾上腺素（NE）活性降低介导了这种无反应性，其作用促进了感觉诱发的觉醒。我们在自由活动的大鼠中使用电生理学、行为学、药理学和光遗传学技术以及听觉刺激来验证这一假设。我们发现，全身降低 NE 信号降低了声音诱发觉醒（SEAs）的概率。睡眠期间 LC 活动的紧张程度预示着 SEAs 的发生。光遗传学 LC 激活促进了觉醒，表现在睡眠-觉醒转换、脑电图去同步化和瞳孔扩张。在声音出现之前进行最小程度的 LC 兴奋增加了 SEA 的概率。使用靶向胞体的阴离子传导型通道视紫红质（stGtACR2）进行 LC 光沉默抑制了 LC 放电并收缩了瞳孔。短暂的 LC 光沉默减少了 SEAs 的概率。因此，LC-NE 活性决定了感觉诱发觉醒的可能性，而其在睡眠期间的降低构成了介导行为无反应性的关键因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa2/7141817/526a2a8de58a/aaz4232-F6.jpg
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