Basal Forebrain Cholinergic Modulation of Sleep Transitions
Basal Forebrain Cholinergic Modulation of Sleep Transitions
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DOI：
10.5665/sleep.4246
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发表时间：
2014-12-01
期刊：
影响因子：
5.6
通讯作者：
de Lecea, Luis
中科院分区：
文献类型：
--
作者：
Irmak, Simal Ozen;de Lecea, Luis
目的：基底前脑胆碱能系统参与需要注意状态、唤醒水平增加和/或与低振幅快速EEG活动相关的皮质激活的认知过程。基底前脑胆碱能间隙内大多数神经元的活动与皮层脑电图及活动状态密切相关。虽然大多数胆碱能神经元在清醒和REM睡眠期间最大程度地放电，但其他类型的基底前脑神经元的活动在不同的唤醒和睡眠状态下有很大差异。许多研究表明基底前脑胆碱能神经元在引起皮质激活和唤醒中的作用。然而，复杂的本地连接内的区域需要使用细胞特异性的操作方法来证明这样的因果关系。设计和测量：在这里，我们结合了光遗传学与表面脑电图记录在自由移动的小鼠，以调查急性胆碱能激活的影响的动态睡眠到觉醒的过渡。我们记录了自然睡眠的动物，并分析了从NREM睡眠到REM睡眠和/或觉醒的过渡，以响应无名质胆碱能神经元的光刺激。我们的研究结果表明，在NREM睡眠期间基底前脑胆碱能神经元的光遗传学激活足以引起皮质激活并促进状态转换，特别是向觉醒和觉醒的转换，在类似于由其他皮层下系统诱导的激活的时间尺度上。我们的研究结果提供了在体细胞特异性的基础前脑胆碱能系统在觉醒和唤醒诱导中的作用。
Objectives: The basal forebrain cholinergic system is involved in cognitive processes that require an attentive state, an increased level of arousal, and/or cortical activation associated with low amplitude fast EEG activity. The activity of most neurons in the basal forebrain cholinergic space is tightly correlated with the cortical EEG and the activity state. While most cholinergic neurons fire maximally during waking and REM sleep, the activity of other types of basal forebrain neurons vastly differs across different arousal and sleep states. Numerous studies have suggested a role for the basal forebrain cholinergic neurons in eliciting cortical activation and arousal. However, the intricate local connectivity within the region requires the use of cell-specific manipulation methods to demonstrate such a causal relationship.Design and Measurements: Here we have combined optogenetics with surface EEG recordings in freely moving mice in order to investigate the effects of acute cholinergic activation on the dynamics of sleep-to-wake transitions. We recorded from naturally sleeping animals and analyzed transitions from NREM sleep to REM sleep and/or wakefulness in response to photo-stimulation of cholinergic neurons in substantia innominata.Results and Conclusions: Our results show that optogenetic activation of basal forebrain cholinergic neurons during NREM sleep is sufficient to elicit cortical activation and facilitate state transitions, particularly transitions to wakefulness and arousal, at a time scale similar to the activation induced by other subcortical systems. Our results provide in vivo cell-specific demonstration for the role of basal forebrain cholinergic system in induction of wakefulness and arousal.