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.

中文翻译：

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Locus coeruleus 去甲肾上腺素活性介导感官诱发的睡眠觉醒。

睡眠的一个决定性特征是对外部刺激的反应性降低，但介导感觉诱发唤醒的机制尚不清楚。我们假设睡眠期间蓝斑 (LC) 去甲肾上腺素 (NE) 活性的降低介导了反应迟钝，其作用促进了感官诱发的觉醒。我们使用电生理学、行为学、药理学和光遗传学技术以及听觉刺激对自由行为的大鼠进行了测试。我们发现 NE 信号的系统性减少降低了声音诱发觉醒 (SEA) 的概率。睡眠期间强直 LC 活动的水平预期 SEA。光遗传学 LC 激活促进了觉醒，这在睡眠-觉醒转换、EEG 不同步和瞳孔扩张中很明显。声音呈现前的最小 LC 激发增加了 SEA 概率。使用靶向胞体的阴离子传导通道视紫红质 (stGtACR2) 的光遗传学 LC 沉默抑制了 LC 尖峰和收缩的瞳孔。短暂的 LC 光沉默降低了 SEA 的可能性。因此，LC-NE 活动决定了感官诱发觉醒的可能性，并且其在睡眠期间的减少是介导行为反应迟钝的关键因素。