In this project, we focus on elucidating how anesthetics interact with the neural network. A small group of neurons from the hypothalamus—orexin/hypocretin neurons—play critical roles in modulating arousal, feeding, stress, and reward. We have shown that activation of orexin neurons with chemogenetic or optogenetic tools facilitates emergence from isoflurane anesthesia and improves analgesia. To visualize the detailed network, we mapped the 3D orexin projections in the mouse brain with confocal and light-sheet microscopies. While manipulating neuronal activities in the mouse brain with optogenetic or chemogenetic tools, we record electroencephalogram, neural calcium activities, and study the animal’s behavior changes. We also study the neuronal properties with electrophysiology and RNAScope tools.