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.
Guillaumin et al. (Sun,) studied this question.
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