Protocol for labeling and manipulating "home"-activated neurons in mice

Home-related cues, such as home bedding, influence affective behaviors in mice, including fear relief, anxiety reduction, and defensive aggression. Here, we present a protocol for labeling and manipulating "home"-activated neurons in the lateral hypothalamus (LH) using a Tet-Off inducible system. We describe steps for virus injection, postoperative recovery, and combining c-Fos-driven activity labeling with chemogenetics. This protocol integrates neuronal targeting with behavioral assays to provide insights into the functional role of "home"-activated neurons in home-driven behavioral adaptations. For complete details on the use and execution of this protocol, please refer to Su et al.¹.