An Inhibitory Lateral Hypothalamic-Preoptic Circuit Mediates Rapid Arousals from Sleep
An Inhibitory Lateral Hypothalamic-Preoptic Circuit Mediates Rapid Arousals from Sleep
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DOI：
10.1016/j.cub.2019.10.026
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发表时间：
2019-12-16
期刊：
影响因子：
9.2
通讯作者：
Fuller, Patrick M.
中科院分区：
文献类型：
--
作者：
Venner, Anne;De Luca, Roberto;Fuller, Patrick M.
在与睡眠-觉醒控制有关的神经元群中，腹外侧视前核（VLPO）已成为关键的睡眠促进中心。然而，迄今为止，调节 VLPO 以控制体内唤醒水平的突触驱动尚未被发现。在这里，我们发现 VLPO 核内促进睡眠的甘丙肽能神经元（从药理学和单细胞转录本分析中定义）是外侧下丘脑 GABA 能（LHGABA）神经元的突触后靶标，并且该通路在体内的激活迅速驱动觉醒。 LHGABA 神经元的 Ca2+ 成像表明它们在清醒状态和快速眼动 (REM) 睡眠状态下均处于活跃状态。与 LHGABA -> VLPO 通路的有效唤醒促进特性一致，LHGABA 神经元的突触前输入源自几个典型的应激和唤醒相关网络节点。这项工作首次证明直接抑制 VLPO 区域的突触可以抑制促进睡眠的神经元，从而快速促进觉醒。
Among the neuronal populations implicated in sleep-wake control, the ventrolateral preoptic (VLPO) nucleus has emerged as a key sleep-promoting center. However, the synaptic drives that regulate the VLPO to control arousal levels in vivo have not to date been identified. Here, we show that sleep-promoting galaninergic neurons within the VLPO nucleus, defined pharmacologically and by single-cell transcript analysis, are postsynaptic targets of lateral hypothalamic GABAergic (LHGABA) neurons and that activation of this pathway in vivo rapidly drives wakefulness. Ca2+ imaging from LHGABA neurons indicate that they are both wake and rapid eye movement (REM)-sleep active. Consistent with the potent arousal-promoting property of the LHGABA -> VLPO pathway, presynaptic inputs to LHGABA neurons originate from several canonical stress- and arousal-related network nodes. This work represents the first demonstration that direct synaptic inhibition of the VLPO area can suppress sleep-promoting neurons to rapidly promote arousal.