Basal forebrain circuit for sleep-wake control

Basal forebrain circuit for sleep-wake control
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DOI:
10.1038/nn.4143
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发表时间:
2015-11-01
影响因子:
25
通讯作者:
Dan, Yang
Dan, Yang
中科院分区:
医学1区
文献类型:
--
作者:
Xu, Min;Chung, Shinjae;Dan, Yang

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哺乳动物的基底前脑在控制睡眠和觉醒中起着重要作用,但其神经回路的研究却很少。我们通过记录和光遗传学干扰四种基因定义的细胞类型在睡眠-觉醒周期中的活动,并通过全面绘制它们的突触连接来检查BF电路。从通道视紫红质-2(ChR 2)标记的神经元的记录显示,三种BF细胞类型,胆碱能,多巴胺能和小清蛋白阳性(PV+)GABA能神经元,在觉醒和快速眼动(REM)睡眠(觉醒/REM活动)比在非REM(NREM)睡眠期间更活跃,并且每种细胞类型的激活迅速诱导觉醒。相反,生长抑素阳性(SOM+)GABA能神经元的激活促进了NREM睡眠,尽管其中只有一些是NREM活跃的。在突触结构上,促醒神经元的兴奋性连接由交感神经-胆碱能-PV+神经元组成,它们均受到SOM+神经元的抑制。总之,这些发现揭示了BF回路用于睡眠-觉醒控制的基本组织。
The mammalian basal forebrain (BF) has important roles in controlling sleep and wakefulness, but the underlying neural circuit remains poorly understood. We examined the BF circuit by recording and optogenetically perturbing the activity of four genetically defined cell types across sleep-wake cycles and by comprehensively mapping their synaptic connections. Recordings from channelrhodopsin-2 (ChR2)-tagged neurons revealed that three BF cell types, cholinergic, glutamatergic and parvalbumin-positive (PV+) GABAergic neurons, were more active during wakefulness and rapid eye movement (REM) sleep (wake/REM active) than during non-REM (NREM) sleep, and activation of each cell type rapidly induced wakefulness. By contrast, activation of somatostatin-positive (SOM+) GABAergic neurons promoted NREM sleep, although only some of them were NREM active. Synaptically, the wake-promoting neurons were organized hierarchically by glutamatergic -> cholinergic -> PV+ neuron excitatory connections, and they all received inhibition from SOM+ neurons. Together, these findings reveal the basic organization of the BF circuit for sleep-wake control.