Department of Biomedical Sciences, Faculty of Biology and Medicine, University of Lausanne, 1005, Lausanne, Switzerland.
Nat Commun. 2020 Nov 27;11(1):6034. doi: 10.1038/s41467-020-19862-y.
Loss of muscle tone triggered by emotions is called cataplexy and is the pathognomonic symptom of narcolepsy, which is caused by hypocretin deficiency. Cataplexy is classically considered to be an abnormal manifestation of REM sleep and is treated by selective serotonin (5HT) reuptake inhibitors. Here we show that deleting the 5HT transporter in hypocretin knockout mice suppressed cataplexy while dramatically increasing REM sleep. Additionally, double knockout mice showed a significant deficit in the buildup of sleep need. Deleting one allele of the 5HT transporter in hypocretin knockout mice strongly increased EEG theta power during REM sleep and theta and gamma powers during wakefulness. Deleting hypocretin receptors in the dorsal raphe neurons of adult mice did not induce cataplexy but consolidated REM sleep. Our results indicate that cataplexy and REM sleep are regulated by different mechanisms and both states and sleep need are regulated by the hypocretinergic input into 5HT neurons.
情绪引发的肌肉张力丧失称为猝倒症，是由下丘脑分泌素缺乏引起的嗜睡症的特征性症状。猝倒症通常被认为是 REM 睡眠的异常表现，可通过选择性 5-羟色胺（5HT）再摄取抑制剂治疗。在这里，我们发现敲除下丘脑分泌素敲除小鼠中的 5HT 转运体可抑制猝倒症，同时大大增加 REM 睡眠。此外，双敲除小鼠的睡眠需求积累明显不足。在下丘脑分泌素敲除小鼠中敲除 5HT 转运体的一个等位基因可强烈增加 REM 睡眠期间的 EEG θ波功率以及觉醒期间的θ波和γ波功率。在成年小鼠的中缝背核神经元中敲除下丘脑分泌素受体不会引起猝倒症，但会巩固 REM 睡眠。我们的结果表明，猝倒症和 REM 睡眠受不同机制调节，状态和睡眠需求均受下丘脑分泌素对 5HT 神经元的输入调节。
