A subset of dorsal raphe dopamine neurons is critical for survival-oriented vigilance

Defensive behaviors are essential for survival, with risk assessment enabling organisms to evaluate and respond to potential threats. The dorsal raphe nucleus (DRN), a key neuromodulatory center, is crucial for encoding motivational salience and regulating arousal and sleep-wake states through its diverse neuronal populations, including dopaminergic neurons (DRN_DA). While the roles of DRN_DAneurons have been studied, their specific contributions to threat evaluation are less understood. Recent research identifies a distinct subset of DRN_DAneurons that express vasoactive intestinal peptide (VIP) and project to the central amygdala (CeA) and the oval nucleus of the bed nucleus of the stria terminalis (ovBNST). Together, these two regions comprise the central extended amygdala, a key network regulating adaptive responses to threats. We hypothesized that distinct DRN_DAsubpopulations exert diverging effects on sleep-wake regulation and that DRN_VIPneurons play a pivotal role in coordinating activity between the CeA and ovBNST, thereby influencing risk assessment and defensive response. To test this hypothesis, we used a combination ofin situhybridization, immunochemistry, whole-brain mapping, electrophysiology, and cell-specific genetic tools in mice and non-human primates. Our findings reveal that DRN_VIPneurons form a key DRN_DAneuronal subset, uniquely positioned to regulate the central extended amygdala through a feedback loop. These neurons receive inputs from Protein Kinase C delta (PKC-δ) neurons in the ovBNST and CeA and send glutamate-releasing projections back to these regions, modulating PKC-δ neuron excitability. Selective ablation of DRN_VIPneurons increases activity in both the BNST and CeA, disrupting active-phase sleep architecture and impairing risk assessment and defensive behaviors. Together, these findings suggest DRN_VIPneurons control specific phases of sleep and orchestrate the central extended amygdala’s role in risk assessment and defensive responses.