Defense or death? A review of the neural mechanisms underlying sensory modality-triggered innate defensive behaviors

Defense or death presents a canonical dilemma for animals when encountering predators. Threatening sensory cues provide essential information that signals predator presence, driving the evolution of a spectrum of defensive behaviors. In rodents, these behaviors, as described by the classic “predatory imminence continuum” model, range from risk assessment and freezing to rapid escape responses. During the pre-encounter phase, risk assessment and avoidance responses are crucial for monitoring the environment with vigilance and cautiousness. Once detected during the post-encounter phase or physically attacked during the circa-strike phase, multiple sensory systems are rapidly activated, triggering escape responses to increase the distance from the threat. Although there are species-specific variations, the brain regions underpinning these defensive strategies, including the thalamus, hypothalamus, and midbrain, are evolutionarily conserved. This review aims to provide a comprehensive overview of the universal innate defensive circuit framework to enrich our understanding of how animals respond to life-threatening situations.