A central alarm system that gates multi-sensory innate threat cues to the amygdala

Perception of threats is essential for survival. Previous findings suggest that parallel pathways independently relay innate threat signals from different sensory modalities to multiple brain areas, such as the midbrain and hypothalamus, for immediate avoidance. Yet little is known about whether and how multi-sensory innate threat cues are integrated and conveyed from each sensory modality to the amygdala, a critical brain area for threat perception and learning. Here, we report that neurons expressing calcitonin gene-related peptide (CGRP) in the parvocellular subparafascicular nucleus in the thalamus and external lateral parabrachial nucleus in the brainstem respond to multi-sensory threat cues from various sensory modalities and relay negative valence to the lateral and central amygdala, respectively. Both CGRP populations and their amygdala projections are required for multi-sensory threat perception and aversive memory formation. The identification of unified innate threat pathways may provide insights into developing therapeutic candidates for innate fear-related disorders. [Display omitted] •CGRPSPFp and CGRPPBel neurons mediate multi-sensory innate threat perception•These neurons send aversive information to different subregions of the amygdala•CGRPSPFp→LA and CGRPPBel→CeA circuits are crucial for aversive memory formation Kang et al. report that two CGRP-expressing neuronal populations in the thalamus and brainstem are activated by innate threat cues from various sensory modalities and are required for their perception. These CGRP neurons relay multi-sensory threat cues to the lateral and central amygdala, forming two parallel pathways for aversive memory formation.