Vasopressin neurons in the paraventricular hypothalamus promote wakefulness via lateral hypothalamic orexin neurons
Vasopressin neurons in the paraventricular hypothalamus promote wakefulness via lateral hypothalamic orexin neurons
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DOI：
10.1016/j.cub.2022.07.020
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发表时间：
2022-09-26
期刊：
影响因子：
9.2
通讯作者：
Mieda, Michihiro
中科院分区：
文献类型：
--
作者：
Islam, Md Tarikul;Rumpf, Florian;Mieda, Michihiro
睡眠-觉醒周期是由复杂的神经网络调节的，这些神经网络包括整个大脑中许多不同的神经元群体。下丘脑室旁核（PVHAVP）中的精氨酸加压素神经元调节各种生理事件和行为，如体液稳态、血压、应激反应、社会互动和进食。唤醒水平的变化往往伴随着这些PVHAVP介导的适应性反应。然而，PVHAVP神经元对睡眠-觉醒调节的贡献仍然未知。在这里，我们报告的参与PVHAVP神经元的唤醒促进。PVHAVP神经元的光遗传刺激迅速诱导从NREM和REM睡眠向觉醒的转变。这种唤醒效应依赖于这些神经元中AVP的表达。同样，PVHAVP神经元的化学发生激活增加了觉醒并减少了NREM和REM睡眠，而这些神经元的化学发生抑制显着减少了觉醒并增加了NREM睡眠。我们观察到PVHAVP神经元在外侧下丘脑中的密集投射与食欲素/下丘脑泌素（LHOrx）神经元的潜在连接。LH中PVHAVP神经元纤维的光遗传刺激立即诱导觉醒，而阻断食欲素受体则显著减弱PVHAVP神经元激活的唤醒作用。单突触狂犬病病毒示踪显示，PVHAVP神经元接受来自参与睡眠-觉醒调节的多个脑区的输入，以及参与应激反应和能量代谢的脑区。此外，PVHAVP神经元介导的唤醒引起的新奇的压力和黑皮质素受体激动剂melanotan-II。因此，我们的数据表明，PVHAVP神经元通过LHOrx神经元在基础睡眠觉醒和一些应激条件下促进觉醒。
The sleep-wakefulness cycle is regulated by complicated neural networks that include many different populations of neurons throughout the brain. Arginine vasopressin neurons in the paraventricular nucleus of the hypothalamus (PVHAVP) regulate various physiological events and behaviors, such as body-fluid homeostasis, blood pressure, stress response, social interaction, and feeding. Changes in arousal level often accompany these PVHAVP-mediated adaptive responses. However, the contribution of PVHAVP neurons to sleep-wakefulness regulation has remained unknown. Here, we report the involvement of PVHAVP neurons in arousal promotion. Optogenetic stimulation of PVHAVP neurons rapidly induced transitions to wakefulness from both NREM and REM sleep. This arousal effect was dependent on AVP expression in these neurons. Similarly, chemogenetic activation of PVHAVP neurons increased wakefulness and reduced NREM and REM sleep, whereas chemogenetic inhibition of these neurons significantly reduced wakefulness and increased NREM sleep. We observed dense projections of PVHAVP neurons in the lateral hypothalamus with potential connections to orexin/hypocretin (LHOrx) neurons. Optogenetic stimulation of PVHAVP neuronal fibers in the LH immediately induced wakefulness, whereas blocking orexin receptors attenuated the arousal effect of PVHAVP neuronal activation drastically. Monosynaptic rabies-virus tracing revealed that PVHAVP neurons receive inputs from multiple brain regions involved in sleep-wakefulness regulation, as well as those involved in stress response and energy metabolism. Moreover, PVHAVP neurons mediated the arousal induced by novelty stress and a melanocortin receptor agonist melanotan-II. Thus, our data suggested that PVHAVP neurons promote wakefulness via LHOrx neurons in the basal sleep-wakefulness and some stressful conditions.