Supramammillary glutamate neurons are a key node of the arousal system.

Supramammillary glutamate neurons are a key node of the arousal system.
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DOI:
10.1038/s41467-017-01004-6
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发表时间:
2017-11-10
影响因子:
16.6
通讯作者:
Fuller PM
Fuller PM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Pedersen NP;Ferrari L;Venner A;Wang JL;Abbott SBG;Vujovic N;Arrigoni E;Saper CB;Fuller PM

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基础和临床观察表明,尾侧下丘脑是上行觉醒系统的一个关键节点,但其背后的细胞类型尚不完全清楚。在这里,我们报道了乳上区谷氨酸释放神经元(SuMvglut2)在化学激活时产生持续的行为和脑电图唤醒。这种影响几乎被废除后,选择性遗传破坏谷氨酸释放从SuMvglut2神经元。SuMvglut2神经元的抑制减弱,唤醒碎片,也抑制θ和γ频率脑电图活动。SuMvglut2神经元包括一个包含谷氨酸和GABA的亚群(SuMvgat/vglut2)和另一个表达一氧化氮合酶的亚群(SuMNos1/ vglut2)。SuMvgat/vglut2神经元的激活产生最小的唤醒,SuMvgat/vglut2末端的光遗传刺激引起单突触向齿状颗粒细胞释放谷氨酸和GABA。SuMNos1/Vglut2神经元的激活能有效地驱动觉醒,而抑制则会减少REM睡眠的θ波活动。这些结果表明SuMvglut2神经元是清醒-睡眠调节系统的关键节点。乳上核(SuM)神经元已经在快速眼动睡眠的背景下进行了研究,但它们在调节觉醒中的可能作用尚不清楚。在这里,作者阐明了三个不同的功能贡献在SuM的电和行为唤醒小鼠使用基因靶向方法。
Basic and clinical observations suggest that the caudal hypothalamus comprises a key node of the ascending arousal system, but the cell types underlying this are not fully understood. Here we report that glutamate-releasing neurons of the supramammillary region (SuMvglut2) produce sustained behavioral and EEG arousal when chemogenetically activated. This effect is nearly abolished following selective genetic disruption of glutamate release from SuMvglut2 neurons. Inhibition of SuMvglut2 neurons decreases and fragments wake, also suppressing theta and gamma frequency EEG activity. SuMvglut2 neurons include a subpopulation containing both glutamate and GABA (SuMvgat/vglut2) and another also expressing nitric oxide synthase (SuMNos1/Vglut2). Activation of SuMvgat/vglut2 neurons produces minimal wake and optogenetic stimulation of SuMvgat/vglut2 terminals elicits monosynaptic release of both glutamate and GABA onto dentate granule cells. Activation of SuMNos1/Vglut2 neurons potently drives wakefulness, whereas inhibition reduces REM sleep theta activity. These results identify SuMvglut2 neurons as a key node of the wake−sleep regulatory system. Supramammillary nucleus (SuM) neurons have been studied in the context of REM sleep but their possible role in mediating wakefulness is not known. Here the authors elucidate the distinct functional contributions of three subpopulations in the SuM on electrographical and behavioral arousal in mice using genetically targeted approaches.
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