The brain undergoes rapid, dramatic, and reversible transitioning between states of wakefulness and unconsciousness during natural sleep and in pathological conditions such as hypoxia, hypotension, and concussion. Transitioning can also be induced pharmacologically using general anesthetic agents. The effect is selective. Mobility, sensory perception, memory formation, and awareness are lost while numerous housekeeping functions persist. How is selective transitioning accomplished? Classically a handful of brainstem and diencephalic “arousal nuclei” have been implicated in driving brain-state transitions on the grounds that their net activity systematically varies with brain state. Here we used transgenic targeted recombination in active populations mice to label neurons active during wakefulness with one reporter and neurons active during pentobarbital-induced general anesthesia with a second, contrasting reporter. We found ‘wake-on’ and ‘anesthesia-on’ neurons in widely distributed regions-of-interest, but rarely encountered neurons labeled with both reporters. Nearly all labeled neurons were either wake-on or anesthesia-on. Thus, anesthesia-on neurons are not unique to the few nuclei discovered to date whose activity appears to increase during anesthesia. Rather neuronal populations selectively active during anesthesia are located throughout the brain where they likely play a causative role in transitioning between wakefulness and anesthesia. The widespread neuronal suppression reported in prior comparisons of the awake and anesthetized brain in animal models and noninvasive imaging in humans reflects only net differences. It misses the ubiquitous presence of neurons whose activity increases during anesthesia. The balance in recruitment of anesthesia-on versus wake-on neuronal populations throughout the brain may be a key driver of regional and global vigilance states.

中文翻译：

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小鼠的麻醉会激活整个大脑中离散的神经元群

在自然睡眠期间以及在缺氧、低血压和脑震荡等病理条件下，大脑会在清醒和无意识状态之间经历快速、剧烈和可逆的转换。也可以使用全身麻醉剂在药理学上诱导转变。效果是选择性的。移动性、感官知觉、记忆形成和意识丧失，而许多家务功能仍然存在。选择性过渡是如何完成的？传统上，少数脑干和间脑“唤醒核”与驱动大脑状态转换有关，因为它们的净活动随着大脑状态而系统地变化。在这里，我们在活跃的小鼠群体中使用转基因靶向重组来标记清醒期间活跃的神经元，其中一位报告者和在戊巴比妥诱导的全身麻醉期间活跃的神经元与另一位对比报告者标记。我们在广泛分布的感兴趣区域中发现了“唤醒”和“麻醉”神经元，但很少遇到带有两个记者标记的神经元。几乎所有标记的神经元都处于唤醒状态或麻醉状态。因此，麻醉神经元并不是迄今为止发现的少数细胞核所独有的，这些细胞核的活动似乎在麻醉期间增加。相反，在麻醉期间选择性活跃的神经元群分布在整个大脑中，它们可能在清醒和麻醉之间的转换中起致病作用。先前在动物模型中比较清醒和麻醉的大脑以及人类的无创成像时报告的广泛的神经元抑制仅反映了净差异。它错过了在麻醉期间活动增加的神经元的普遍存在。在整个大脑中招募麻醉与唤醒神经元群体的平衡可能是区域和全球警戒状态的关键驱动因素。