Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC 29425.
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC 29425
eNeuro. 2020 Apr 29;7(2). doi: 10.1523/ENEURO.0017-20.2020. Print 2020 Mar/Apr.
Hypothalamic orexin (hypocretin, HCRT) deficiency causes sleep disorder narcolepsy with cataplexy in humans and murine. As another integral group of sleep/wake-regulating neurons in the same brain area, the melanin-concentrating hormone (MCH) neurons' involvement in cataplexy remains ambiguous. Here we used the live animal deep-brain calcium (Ca) imaging tool to record MCH neuron dynamics during cataplexy by expressing calcium sensor GCaMP6s into genetically defined MCH neurons in orexin knock-out mice, which are a model of human narcolepsy. Similar to wild-type mice, MCH neurons of the narcoleptic mice displayed significantly higher Ca transient fluorescent intensity during rapid eye movement (REM) sleep and active waking (AW) episodes compared with non-REM (NREM) sleep. Moreover, MCH neurons displayed significantly lower Ca signals during cataplexy. Importantly, a pre-cataplexy elevation of Ca signals from MCH neurons was not a prerequisite for cataplexy initiation. Our results demonstrated the inactivation status of MCH neurons during cataplexy and suggested that MCH neurons are not involved in the initiation and maintenance of cataplexy in orexin knock-out mice.
下丘脑食欲素（Hypocretin，HCRT）缺乏会导致人类和鼠类的睡眠障碍性嗜睡症伴猝倒。作为同一脑区中另一组重要的睡眠/觉醒调节神经元，黑皮质素浓缩激素（Melanin-concentrating hormone，MCH）神经元在猝倒中的作用仍不明确。在这里，我们使用活体动物深部脑钙（Ca）成像工具，通过在食欲素敲除小鼠中表达钙传感器 GCaMP6s 到遗传定义的 MCH 神经元，记录了猝倒期间 MCH 神经元的动力学。与野生型小鼠相似，在快速眼动（REM）睡眠和活跃觉醒（AW）期间，嗜睡症小鼠的 MCH 神经元的 Ca 瞬态荧光强度显著高于非快速眼动（NREM）睡眠。此外，MCH 神经元在猝倒期间显示出明显较低的 Ca 信号。重要的是，MCH 神经元的 Ca 信号在猝倒前升高并不是猝倒发作的必要条件。我们的结果表明，在猝倒期间 MCH 神经元处于失活状态，并提示 MCH 神经元不参与食欲素敲除小鼠猝倒的发作和维持。
