# Dorsal Raphe VIP Neurons Are Critical for Survival‐Oriented Vigilance

## TL;DR

This study identifies a specific type of neuron in the brain that helps regulate sleep and defensive behaviors in response to threats.

## Contribution

The study reveals the critical role of DRNVIP neurons in threat processing and sleep regulation through novel neural feedback loops.

## Key findings

- DRNVIP neurons form feedback loops with PKC-δ neurons in the CeA and ovBNST.
- Ablation of DRNVIP neurons disrupts sleep and impairs defensive responses.
- DRNVIP neurons are activated by visual threat cues in behaving mice.

## 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 (DRNDA) 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 DRNVIP 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 DRNVIP neurons form a distinct feedback loop with PKC‐δ neurons in the CeA and ovBNST. These DRNVIP neurons release glutamate and modulate excitability in target regions. Selective ablation of DRNVIP 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 DRNVIP neurons during presentation of the visual threat‐predictive cue in behaving mice. These results suggest that DRNVIP neurons regulate specific sleep phases and control defensive behaviors, acting as a neuronal alarm system that responds to threats.

DRNVIP neurons in mice and primates are strategically positioned to influence the central extended amygdala via feedback loops. They regulate the excitability of PKC‐δ neurons in the ovBNST and CeA through glutamate release. Their ablation heightens activity in these regions, disrupts active‐phase sleep architecture, enhances risk assessment behaviors that may reflect dysfunctional processing, and alters defensive responses.