Dorsal Raphe VIP Neurons Are Critical for Survival‐Oriented Vigilance

ABSTRACT Defensive behaviors are essential for survival, relying on risk assessment to detect and respond to threats. The dorsal raphe nucleus (DRN), a brain region involved in sleep‐wake regulation, contains dopaminergic neurons (DRN _DA ) with unclear roles in threat evaluation. A subset of these neurons expresses vasoactive‐intestinal‐peptide (VIP) and projects to two key regions for adaptive threat responses: the central amygdala (CeA) and the oval nucleus of the bed nucleus of the stria terminalis (ovBNST). We hypothesized that DRN _VIP neurons modulate sleep‐wake regulation and play a pivotal role in coordinating activity between the CeA and ovBNST, thereby influencing risk assessment and defensive response. We found that DRN _VIP neurons form a distinct feedback loop with PKC‐δ neurons in the CeA and ovBNST. These DRN _VIP neurons release glutamate and modulate excitability in target regions. Selective ablation of DRN _VIP neurons disrupts active‐phase sleep architecture, enhances risk assessment behaviors that may reflect dysfunctional processing, and impairs defensive responses. Fiber‐photometry revealed direct activation of the DRN _VIP neurons during presentation of the visual threat‐predictive cue in behaving mice. These results suggest that DRN _VIP neurons regulate specific sleep phases and control defensive behaviors, acting as a neuronal alarm system that responds to threats.