Sleep Homeostasis Modulates Hypocretin-Mediated Sleep-to-Wake Transitions
Sleep Homeostasis Modulates Hypocretin-Mediated Sleep-to-Wake Transitions
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DOI：
10.1523/jneurosci.1205-09.2009
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发表时间：
2009-09-02
影响因子：
5.3
通讯作者：
de Lecea, Luis
中科院分区：
文献类型：
--
作者：
Carter, Matthew E.;Adamantidis, Antoine;de Lecea, Luis
下丘脑泌素（hypocretins，Hcrts）是下丘脑外侧区表达的两种神经肽，对清醒的稳定性起着至关重要的作用。以前，我们的实验室证明，在体内光刺激Hcrt神经元的基因靶向ChR 2，光激活阳离子通道，足以增加觉醒事件的概率在慢波睡眠和快速眼动睡眠。在目前的研究中，我们想知道Hcrt介导的睡眠-觉醒转换是否受到亮/暗周期和睡眠压力的影响。我们发现，Hcrt神经元的刺激增加了觉醒事件的概率在整个光/暗期间，但这种效果被减少与睡眠压力引起的2或4小时的睡眠剥夺。有趣的是，光刺激Hcrt神经元仍然足以增加活动评估c-Fos表达Hcrt神经元睡眠剥夺后，虽然这种刺激并没有导致增加的过渡到觉醒。此外，我们发现，光刺激Hcrt神经元增加神经活动评估c-Fos表达的下游唤醒促进蓝斑和结节乳头状核，但不经过2小时的睡眠剥夺。最后，刺激Hcrt神经元仍然足以增加组氨酸脱羧酶缺陷敲除动物的觉醒事件的概率。总的来说，这些结果表明，Hcrt系统通过激活多个下游靶点来促进整个明/暗期间的觉醒，这些靶点本身随着睡眠压力的增加而被抑制。
The hypocretins (Hcrts) (also called orexins) are two neuropeptides expressed in the lateral hypothalamus that play a crucial role in the stability of wakefulness. Previously, our laboratory demonstrated that in vivo photostimulation of Hcrt neurons genetically targeted with ChR2, a light-activated cation channel, was sufficient to increase the probability of an awakening event during both slow-wave sleep and rapid eye movement sleep. In the current study, weask whether Hcrt-mediated sleep-to-wake transitions are affected by light/dark period and sleep pressure. We found that stimulation of Hcrt neurons increased the probability of an awakening event throughout the entire light/dark period but that this effect was diminished with sleep pressure induced by 2 or 4 h of sleep deprivation. Interestingly, photostimulation of Hcrt neurons was still sufficient to increase activity assessed by c-Fos expression in Hcrt neurons after sleep deprivation, although this stimulation did not cause an increase in transitions to wakefulness. In addition, we found that photostimulation of Hcrt neurons increases neural activity assessed by c-Fos expression in the downstream arousal-promoting locus ceruleus and tuberomammilary nucleus but not after 2 h of sleep deprivation. Finally, stimulation of Hcrt neurons was still sufficient to increase the probability of an awakening event in histidine decarboxylase-deficient knock-out animals. Collectively, these results suggest that the Hcrt system promotes wakefulness throughout the light/dark period by activating multiple downstream targets, which themselves are inhibited with increased sleep pressure.