The NAergic locus coeruleus- ventrolateral preoptic area neural circuit mediates rapid arousal from sleep
The NAergic locus coeruleus- ventrolateral preoptic area neural circuit mediates rapid arousal from sleep
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DOI：
10.1016/j.cub.2021.06.031
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发表时间：
2021-09-13
期刊：
影响因子：
9.2
通讯作者：
Zhang, Ling
中科院分区：
文献类型：
--
作者：
Liang, Yue;Shi, Wu;Zhang, Ling
位于脑干的蓝斑（LC）在促进觉醒中起着重要作用。然而，这种功能背后的神经回路仍然不清楚。使用皮层脑电图结合光极记录，我们发现，LC去甲肾上腺素能（LCNA）神经元在觉醒期间表现出高活性，而抑制这些神经元的活性会导致觉醒减少。病毒示踪显示，LCNA神经元直接投射到腹外侧视前区（VLPO），去甲肾上腺素能（NA能）LC-VLPO（NA能LC-VLPO）神经回路的光遗传激活促进唤醒。VLPO中的光极记录揭示了响应于LCNA神经元的光遗传学激活而被刺激的两个功能不同的神经元群体。一致地，我们确定了两种类型的VLPO神经元，表现出不同的反应，从LC介导的离散肾上腺素能受体的NA能投射。总之，我们的研究结果表明，NAergicLC-VLPO神经回路是控制觉醒的关键途径，并且通过α（2）受体抑制VLPO中的睡眠活性神经元和通过α（1）和β受体激活VLPO中的唤醒活性神经元产生协同效应。
The locus coeruleus (LC), which is located in the brain stem, plays an important role in promoting arousal. However, the neural circuitry underlying this function remains unclear. Using cortical electroencephalography combined with optrode recording, we found that LC noradrenergic (LCNA) neurons exhibit high activity during wakefulness, while suppressing the activity of these neurons causes a reduction in wakefulness. Viral tracing showed that LCNA neurons directly project to the ventrolateral preoptic area (VLPO) and that optogenetic activation of the noradrenergic (NAergic) LC-VLPO (NAergicLC-VLPO) neural circuit promotes arousal. Optrode recordings in the VLPO revealed two functionally distinct neuronal populations that were stimulated in response to the optogenetic activation of LCNA neurons. Consistently, we identified two types of VLPO neurons that exhibited different responses to NAergic projections from the LC mediated by discrete adrenergic receptors. Together, our results demonstrate that the NAergicLC-VLPO neural circuit is a critical pathway for controlling wakefulness and that a synergistic effect is produced by inhibition of sleep-active neurons in the VLPO through alpha(2) receptors and activation of wake-active neurons in the VLPO through alpha(1) and beta receptors.