Normal sleep–wake behavior is extremely important for humans to maintain basic physiological and cognitive activities. However, the neural mechanisms underlying sleep–wake regulation are not fully understood. The paraventricular nucleus (PVN) of the hypothalamus has been classically defined as a region for the regulation of the hypothalamoneurohypophysial system and autonomic nervous system. Here, we identify the glutamatergic neurons in the PVN that play a unique role in sleep–wake regulation. Firstly using in vivo fiber photometry, we found altered calcium activities of PVN glutamatergic neurons during three sleep state transitions in freely behaving mice. The calcium activities of PVN glutamatergic neurons began to increase before non-rapid-eye movement (NREM) sleep to wake transitions and NREM sleep to rapid-eye-movement (REM) sleep transitions and began to decrease before wake to NREM sleep transitions. Then we used chemogenetic manipulations together with polysomnographic recordings, activation of PVN neurons increased wakefulness and decreased NREM sleep, while inhibition of PVN neurons caused a reduction in wakefulness and an increase in NREM sleep. Altogether, our findings revealed an important role for PVN glutamatergic neurons in the regulation of wake state.

正常的觉醒行为对于人类维持基本的生理和认知活动极为重要。然而，对睡眠-唤醒调节的神经机制尚未完全了解。下丘脑的室旁核（PVN）已被经典地定义为调节下丘脑神经下垂体系统和自主神经系统的区域。在这里，我们确定了PVN中的谷氨酸能神经元在睡眠-觉醒调节中起着独特的作用。首先在体内使用纤维光度法，我们发现在行为自由的小鼠的三个睡眠状态转换过程中，PVN谷氨酸能神经元的钙活性发生了改变。PVN谷氨酸能神经元的钙活性在非快速眼动（NREM）睡眠到觉醒转变和NREM睡眠到快速眼动（REM）睡眠转变之前开始增加，并在觉醒到NREM睡眠转变之前开始减少。然后，我们使用了化学发生学操作以及多导睡眠图记录，激活了PVN神经元，增加了清醒并减少了NREM睡眠，而抑制PVN神经元导致了清醒的减少和NREM睡眠的增加。总之，我们的发现揭示了PVN谷氨酸能神经元在唤醒状态调节中的重要作用。