Paraventricular hypothalamic nucleus are essential for arousal promotion and maintenance

Adequate wakefulness is fundamental for proper daytime functioning. Clinical observations indicate that the paramedian region of the hypothalamus is a critical node for controlling wakefulness. However, the specific nucleus and neural circuitry for this function remain unknown. Here, we found that inhibition of PVHvglut2 neurons induced 3-h increase of NREM sleep. Chemogenetic activation of PVHvglut2 neurons potently induced 9-h wakefulness, and PVHCRH neuronal activation also exerted wakefulness. Photostimulation of PVHvglut2→parabrachial complex/ventral lateral septum circuits immediately drove transitions from NREM to wakefulness. Furthermore, using in vivo fiber photometry or multichannel electrophysiological recordings in mice, we find arousal-dependent increases in population activity of PVHvglut2 neurons. Most importantly, ablation of PVHvglut2 neurons dramatically led mice to hypersomnia-like behaviors. These results demonstrate that PVHvglut2 neurons are essential for physiologic arousal in the hypothalamus.