Hung Chi Jung, Ono Daisuke, Kilduff Thomas S, Yamanaka Akihiro
Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Elife. 2020 Apr 21;9:e54275. doi: 10.7554/eLife.54275.
Orexin/hypocretin-producing and melanin-concentrating hormone-producing (MCH) neurons are co-extensive in the hypothalamus and project throughout the brain to regulate sleep/wakefulness. Ablation of orexin neurons decreases wakefulness and results in a narcolepsy-like phenotype, whereas ablation of MCH neurons increases wakefulness. Since it is unclear how orexin and MCH neurons interact to regulate sleep/wakefulness, we generated transgenic mice in which both orexin and MCH neurons could be ablated. Double-ablated mice exhibited increased wakefulness and decreased both rapid eye movement (REM) and non-REM (NREM) sleep. Double-ablated mice showed severe cataplexy compared with orexin neuron-ablated mice, suggesting that MCH neurons normally suppress cataplexy. Double-ablated mice also showed frequent sleep attacks with elevated spectral power in the delta and theta range, a unique state that we call 'delta-theta sleep'. Together, these results indicate a functional interaction between orexin and MCH neurons in vivo that suggests the synergistic involvement of these neuronal populations in the sleep/wakefulness cycle.
产生食欲素/下丘脑泌素和产生黑色素聚集激素（MCH）的神经元在下丘脑中共同分布，并投射到整个大脑以调节睡眠/觉醒。食欲素神经元的消融会减少觉醒并导致发作性睡病样表型，而MCH神经元的消融会增加觉醒。由于目前尚不清楚食欲素和MCH神经元如何相互作用以调节睡眠/觉醒，我们培育了一种转基因小鼠，其中食欲素和MCH神经元都可以被消融。双消融小鼠表现出觉醒增加，快速眼动（REM）睡眠和非快速眼动（NREM）睡眠均减少。与食欲素神经元消融小鼠相比，双消融小鼠表现出严重猝倒，这表明MCH神经元通常会抑制猝倒。双消融小鼠还表现出频繁的睡眠发作，在δ和θ范围内频谱功率升高，这是一种我们称为“δ-θ睡眠”的独特状态。总之，这些结果表明食欲素和MCH神经元在体内存在功能相互作用，提示这些神经元群体协同参与睡眠/觉醒周期。
