Optogenetic stimulation of c1 and retrotrapezoid nucleus neurons causes sleep state-dependent cardiorespiratory stimulation and arousal in rats.
Optogenetic stimulation of c1 and retrotrapezoid nucleus neurons causes sleep state-dependent cardiorespiratory stimulation and arousal in rats.
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DOI：
10.1161/hypertensionaha.111.00860
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Guyenet PG
中科院分区：
文献类型：
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作者：
Abbott SB;Coates MB;Stornetta RL;Guyenet PG
C1儿茶酚胺能神经元和后斜方核的神经元是脑干网络内的整合节点，调节由缺氧和高碳酸血症引起的心肺反射，这些刺激也产生睡眠唤醒。在本研究中，将视紫红质2选择性地引入这些神经元中，以确定它们的选择性激活是否也会在睡眠大鼠中产生唤醒。睡眠阶段确定脑电图和颈部肌肉肌电图记录。使用无限制的全身体积描记法测量呼吸，并通过遥测测量血压。在非快速眼动睡眠期间，C1区的单侧光刺激在83.0 ± 14.7%的试验中引起觉醒，并立即引起强烈的心肺激活。在快速眼动睡眠期间也观察到光刺激期间的唤醒（41.9 ± 5.6%的试验），但可靠性低于非快速眼动睡眠期间。光刺激引起的心肺反应在快速眼动睡眠期间比非快速眼动睡眠或清醒时明显更小。系统性α 1肾上腺素受体阻滞剂减少光刺激的心肺效应，但对非快速眼动睡眠期间由光刺激引起的觉醒没有影响。死后组织学显示，表达视紫红质2-mCherry的神经元主要是儿茶酚胺能神经元（81%）。这些结果表明，选择性激活C1和后斜方核神经元产生状态依赖性唤醒和心肺刺激。这些神经元被化学感受器刺激强烈激活，可能导致与阻塞性睡眠呼吸暂停相关的睡眠中断。
C1 catecholaminergic neurons and neurons of the retrotrapezoid nucleus are integrative nodes within the brainstem network regulating cardiorespiratory reflexes elicited by hypoxia and hypercapnia, stimuli that also produce arousal from sleep. In the present study, Channelrhodopsin2 was selectively introduced into these neurons with a lentiviral vector in order to determine if their selective activation also produces arousal in sleeping rats. Sleep stages were identified from electroencephalographic and neck muscle electromyographic recordings. Breathing was measured using unrestrained whole body plethysmography and blood pressure by telemetry. During non-rapid eye movement sleep, unilateral photostimulation of the C1 region caused arousal in 83.0 ± 14.7% of trials and immediate and intense cardiorespiratory activation. Arousal during photostimulation was also observed during rapid eye movement sleep (41.9 ± 5.6% of trials), but less reliably than during non-rapid eye movement sleep. The cardiorespiratory responses elicited by photostimulation were dramatically smaller during rapid eye movement sleep than non-rapid eye movement sleep or wakefulness. Systemic alpha1-adrenoreceptor blockade reduced the cardiorespiratory effects of photostimulation, but had no effect on the arousal caused by photostimulation during non-rapid eye movement sleep. Postmortem histology showed that neurons expressing Channelrhodopsin2-mCherry were predominantly catecholaminergic (81%). These results show that selective activation of C1 and retrotrapezoid nucleus neurons produces state dependent arousal and cardiorespiratory stimulation. These neurons, which are powerfully activated by chemoreceptor stimulation, may contribute to the sleep disruption associated with obstructive sleep apnea.