The hypothalamic supramammillary nucleus (SuM) plays a crucial role in controlling wakefulness, but the downstream target regions participating in this control process remain unknown. Here, using circuit-specific fiber photometry and single-neuron electrophysiology together with electroencephalogram, electromyogram and behavioral recordings, we find that approximately half of SuM neurons that project to the medial septum (MS) are wake-active. Optogenetic stimulation of axonal terminals of SuM-MS projection induces a rapid and reliable transition to wakefulness from non-rapid-eye movement or rapid-eye movement sleep, and chemogenetic activation of SuM^MS projecting neurons significantly increases wakefulness time and prolongs latency to sleep. Consistently, chemogenetically inhibiting these neurons significantly reduces wakefulness time and latency to sleep. Therefore, these results identify the MS as a functional downstream target of SuM and provide evidence for the modulation of wakefulness by this hypothalamic-septal projection.

下丘脑乳头上核（SuM）在控制觉醒方面发挥着至关重要的作用，但参与这一控制过程的下游目标区域仍然未知。在这里，使用特定电路的光纤光度测量和单神经元电生理学以及脑电图、肌电图和行为记录，我们发现投射到内侧隔膜 (MS) 的 SuM 神经元中大约一半是唤醒活动的。 SuM-MS 投射的轴突末端的光遗传学刺激诱导从非快速眼动或快速眼动睡眠快速可靠地转变为觉醒，而 SuM ^MS投射神经元的化学遗传学激活显着增加了觉醒时间并延长了睡眠潜伏期。一致地，通过化学遗传学方法抑制这些神经元可以显着减少觉醒时间和睡眠潜伏期。因此，这些结果将 MS 确定为 SuM 的功能性下游目标，并为这种下丘脑-间隔投射调节觉醒提供了证据。