Selective Activation of Cholinergic Basal Forebrain Neurons Induces Immediate Sleep-wake Transitions

Selective Activation of Cholinergic Basal Forebrain Neurons Induces Immediate Sleep-wake Transitions
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选择性激活胆碱能基底前脑神经元诱导立即睡眠-觉醒转变

DOI:
10.1016/j.cub.2014.02.011
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发表时间:
2014-03-17
期刊:
影响因子:
9.2
通讯作者:
Yu, Yan-qin
Yu, Yan-qin
中科院分区:
生物学1区
文献类型:
--
作者:
Han, Yong;Shi, Yu-feng;Yu, Yan-qin

文献摘要

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基底前脑 (BF) 在皮质激活中发挥着至关重要的作用 [1, 2]。然而,胆碱能 BF (ch-BF) 神经元在睡眠-觉醒周期中的确切作用仍不清楚 [3, 4]。我们证明,用视紫红质通道蛋白 2 (ChR2) 基因靶向的 ch-BF 神经元的光刺激足以诱导从慢波睡眠 (SWS) 立即过渡到清醒或快速眼动 (REM) 睡眠。光刺激最有可能在 SWS 期间诱导行为唤醒,但在 REM 睡眠期间则不然,这一结果与之前报道的去甲肾上腺素能或下丘脑分泌素神经元的光刺激诱导 SWS 和 REM 睡眠中的唤醒转变形成鲜明对比。此外,光诱导的从 SWS 到清醒或 REM 睡眠的转变的比率与自然转变的比率没有显着差异,这表明 ch-BF 神经元的激活促进了从 SWS 的转变,但不会改变转变的方向。清醒或快速眼动睡眠期间 ch-BF 神经元的兴奋维持了皮质激活。刺激这些神经元 1 小时会导致随后的非活动期的清醒持续时间延迟增加。我们的结果表明,仅激活 ch-BF 神经元就足以抑制 SWS 并促进觉醒和 REM 睡眠。
The basal forebrain (BF) plays a crucial role in cortical activation [1, 2]. However, the exact role of cholinergic BF (ch-BF) neurons in the sleep-wake cycle remains unclear [3, 4]. We demonstrated that photostimulation of ch-BF neurons genetically targeted with channelrhodopsin 2 (ChR2) was sufficient to induce an immediate transition to waking or rapid eye movement (REM) sleep from slow-wave sleep (SWS). Light stimulation was most likely to induce behavioral arousal during SWS, but not during REM sleep, a result in contrast to the previously reported photostimulation of noradrenergic or hypocretin neurons that induces wake transitions from both SWS and REM sleep. Furthermore, the ratio of light-induced transitions from SWS to wakefulness or to REM sleep did not significantly differ from that of natural transitions, suggesting that activation of ch-BF neurons facilitates the transition from SWS but does not change the direction of the transition. Excitation of ch-BF neurons during wakefulness or REM sleep sustained the cortical activation. Stimulation of these neurons for 1 hr induced a delayed increase in the duration of wakefulness in the subsequent inactive period. Our results suggest that activation of ch-BF neurons alone is sufficient to suppress SWS and promote wakefulness and REM sleep.