Unified neural pathways that gate affective pain and multisensory innate threat signals to the amygdala

Abstract Perception of aversive sensory stimuli such as pain and innate threat cues is essential for animal survival. The amygdala is critical for aversive sensory perception, and it has been suggested that multiple parallel pathways independently relay aversive cues from each sensory modality to the amygdala. However, a convergent pathway that relays multisensory aversive cues to the amygdala has not been identified. Here, we report that neurons expressing calcitonin gene-related peptide (CGRP) in the parvocellular subparafasicular thalamic nucleus (SPFp) are necessary and sufficient for affective-motivational pain perception by forming a spino-thalamo-amygdaloid pain pathway. In addition, we find that this thalamic CGRP pain pathway, together with well-known parabrachio-amygdaloid CGRP pain pathway, relays multisensory innate threat cues to the amygdala. The discovery of unified pathways that collectively gate aversive sensory stimuli from all sensory modalities may provide critical circuit-based insights for developing therapeutic interventions for affective pain- and innate fear-related disorders.