Lee Maan Gee, Hassani Oum K, Jones Barbara E
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
J Neurosci. 2005 Jul 13;25(28):6716-20. doi: 10.1523/JNEUROSCI.1887-05.2005.
Although maintained by multiple arousal systems, wakefulness falters if orexin (hypocretin), orexin receptors, or orexin neurons are deficient; narcolepsy results with hypersomnolence or sudden onset of rapid eye movement sleep [or paradoxical sleep (PS)] and loss of muscle tonus. To learn how orexin neurons maintain wakefulness, we recorded neurons in head-fixed rats across the sleep-waking cycle and then labeled them with Neurobiotin to identify them by immunohistochemistry. We show that identified orexin neurons discharge during active waking, when postural muscle tone is high in association with movement, decrease discharge during quiet waking in absence of movement, and virtually cease firing during sleep, when postural muscle tone is low or absent. During PS, they remain relatively silent in association with postural muscle atonia and most often despite phasic muscular twitches. They increase firing before the end of PS and thereby herald by several seconds the return of waking and muscle tone. The orexin neurons would thus stimulate arousal, while antagonizing sleep and muscle atonia.
尽管觉醒由多个唤醒系统维持，但如果食欲素（下丘脑泌素）、食欲素受体或食欲素神经元缺乏，觉醒就会出现障碍；发作性睡病会导致嗜睡或快速眼动睡眠[或异相睡眠（PS）]突然发作以及肌肉张力丧失。为了了解食欲素神经元如何维持觉醒，我们在头部固定的大鼠睡眠-觉醒周期中记录神经元，然后用神经生物素标记它们，以便通过免疫组织化学鉴定它们。我们发现，已鉴定的食欲素神经元在主动觉醒期间放电，此时与运动相关的姿势肌肉张力较高，在无运动的安静觉醒期间放电减少，而在睡眠期间，当姿势肌肉张力较低或不存在时，几乎停止放电。在PS期间，它们与姿势性肌肉张力缺失相关，并且尽管有阶段性肌肉抽搐，但通常仍保持相对沉默。它们在PS结束前增加放电，从而在数秒前预示觉醒和肌肉张力的恢复。因此，食欲素神经元会刺激觉醒，同时对抗睡眠和肌肉张力缺失。
