Control of REM sleep by ventral medulla GABAergic neurons.
Control of REM sleep by ventral medulla GABAergic neurons.
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DOI：
10.1038/nature14979
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发表时间：
2015-10-15
期刊：
影响因子：
64.8
通讯作者：
Dan Y
中科院分区：
文献类型：
--
作者：
Weber F;Chung S;Beier KT;Xu M;Luo L;Dan Y
快速眼动（REM）睡眠是一种独特的大脑状态，其特征是激活的脑电图（EEG）和完全的骨骼肌麻痹，并且它与生动的梦有关。Jouvet的横断研究首先证明脑干对于REM睡眠的产生是必要的和充分的，并且脑桥中的神经回路已经被广泛研究。延髓也包含在REM睡眠期间活跃的神经元，但它们是否在REM睡眠产生中发挥因果作用仍不清楚。在这里，我们表明，GABA能通路起源于腹侧延髓（vM）有力地促进REM睡眠。vM GABA能神经元的光遗传激活快速可靠地启动REM睡眠发作并延长其持续时间，而灭活这些神经元则具有相反的效果。视紫红质通道2（ChR 2）标记的vM GABA能神经元的光电极记录显示，它们在REM睡眠（REM-max）期间最活跃，在清醒期间，它们在进食和梳理期间优先活跃。此外，双逆行追踪表明，头侧的投射到脑桥和中脑和尾侧的投射到脊髓起源于单独的VM神经元群体。激活嘴侧GABA能投射足以诱导和维持REM睡眠，这可能部分地通过抑制腹外侧导水管周围灰质（vlPAG）中的REM抑制性GABA能神经元来介导。这些结果确定了控制REM睡眠的脑桥延髓网络的关键组成部分。根据指令诱导REM睡眠的能力可能为研究其功能提供了一个强大的工具。
Rapid eye movement (REM) sleep is a distinct brain state characterized by activated electroencephalogram (EEG) and complete skeletal muscle paralysis, and it is associated with vivid dreams. Transection studies by Jouvet first demonstrated that the brainstem is both necessary and sufficient for REM sleep generation, and the neural circuits in the pons have since been studied extensively. The medulla also contains neurons that are active during REM sleep, but whether they play a causal role in REM sleep generation remains unclear. Here we show that a GABAergic pathway originating from the ventral medulla (vM) powerfully promotes REM sleep. Optogenetic activation of vM GABAergic neurons rapidly and reliably initiated REM sleep episodes and prolonged their durations, whereas inactivating these neurons had the opposite effects. Optrode recordings from channelrhodopsin 2 (ChR2)-tagged vM GABAergic neurons showed that they were most active during REM sleep (REM-max), and during wakefulness they were preferentially active during eating and grooming. Furthermore, dual retrograde tracing showed that the rostral projections to the pons and midbrain and caudal projections to the spinal cord originate from separate vM neuron populations. Activating the rostral GABAergic projections was sufficient for both the induction and maintenance of REM sleep, which are likely mediated in part by inhibition of REM-suppressing GABAergic neurons in the ventrolateral periaqueductal gray (vlPAG). These results identify a key component of the pontomedullary network controlling REM sleep. The capability to induce REM sleep on command may offer a powerful tool for investigating its functions.