Activation of Preoptic Tachykinin 1 Neurons Promotes Wakefulness over Sleep and Volatile Anesthetic-Induced Unconsciousness.
Activation of Preoptic Tachykinin 1 Neurons Promotes Wakefulness over Sleep and Volatile Anesthetic-Induced Unconsciousness.
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旋转前旋转蛋白1神经元的激活促进了睡眠和挥发性麻醉引起的无意识性的清醒。
DOI：
10.1016/j.cub.2020.10.050
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发表时间：
2021-01-25
期刊：
影响因子：
--
通讯作者：
Kelz MB
中科院分区：
文献类型：
--
作者：
Reitz SL;Wasilczuk AZ;Beh GH;Proekt A;Kelz MB
内源性睡眠和全身麻醉是具有相似特征的不同状态。神经科学特别感兴趣的是伴随这两种状态的意识丧失。多种证据表明，全身麻醉剂可以利用调节唤醒的神经回路来产生无意识。然而，关于神经回路，更具体地说，塑造睡眠和觉醒的相同神经元是否真的影响体内的麻醉状态，仍然存在争议。下丘脑视前区（POA）神经元密切参与调节自发性和麻醉诱导的觉醒变化。然而，最近的研究表明，能够调节内源性睡眠的POA GABA能或多巴胺能神经元不能影响麻醉的开始或消散。我们假设，POA的广泛的神经元多样性可能掩盖了一个子集的神经元在调节唤醒和麻醉的收敛作用。与先前发表的报告相反，我们表明，POA Tac 1神经元的化学发生激活消除了NREM和REM睡眠，强烈巩固了清醒状态数小时，即使在一段时间内睡眠驱动力升高。此外，Tac 1 POA神经元的化学发生激活可稳定异氟烷和七氟烷诱导的清醒状态。Tac 1激活的小鼠显示出对进入异氟烷麻醉的部分抵抗，以及退出异氟烷和七氟烷诱导的无意识状态的更明显的能力。我们的结论是，POA Tac 1神经元可以有效地加强对内源性和药物诱导的无意识状态的唤醒。因此，POA Tac 1神经元增加了在全身麻醉状态下唤醒调节系统参与的因果支持。同样的神经元在睡眠和麻醉中调节唤醒的程度还不清楚。雷茨等人描述了一群表达Tac 1的POA神经元，当被激活时，它们增强了对自然睡眠和麻醉诱导的无意识的唤醒;证实了调节内源性唤醒的神经元形成了麻醉状态。
Endogenous sleep and general anesthesia are distinct states that share similar traits. Of particular interest to neuroscience is the loss of consciousness that accompanies both states. Multiple lines of evidence demonstrate that general anesthetics can coopt the neural circuits regulating arousal to produce unconsciousness. However, controversy remains as to whether the neural circuits, and more specifically, the same neurons shaping sleep and wakefulness actually do influence the anesthetic state in vivo. Hypothalamic preoptic area (POA) neurons are intimately involved in modulating spontaneous and anesthetic-induced changes in arousal. Nevertheless, recent work suggests that POA GABAergic or glutamatergic neurons capable of regulating endogenous sleep fail to influence the onset or dissipation of anesthesia. We hypothesized that the POA’s broad neuronal diversity could mask convergent roles of a subset of neurons in regulating both arousal and anesthesia. Contrary to a previously published report, we show that chemogenetic activation of POA Tac1 neurons obliterates both NREM and REM sleep, strongly consolidating the waking state for hours, even during a period of elevated sleep drive. Moreover, chemogenetic activation of Tac1 POA neurons stabilizes the wake state against both isoflurane- and sevoflurane-induced unconsciousness. Tac1 activated mice display a partial resistance to entering isoflurane anesthesia and a more pronounced ability to exit both isoflurane and sevoflurane induced-unconscious states. We conclude that POA Tac1 neurons can potently reinforce arousal both against endogenous and drug-induced unconscious states. POA Tac1 neurons thus add causal support for the involvement of arousal-regulating systems in the state of general anesthesia. The degree to which the same neurons modulate arousal in both sleep and anesthesia is unclear. Reitz et al. describe a population of Tac1-expressing POA neurons that when activated, reinforce arousal against both natural sleep and anesthetic-induced unconsciousness; confirming that neurons modulating endogenous arousal shape states of anesthesia.
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