Abstract

Recent studies suggest that the neurons expressing calcitonin gene-related peptide (CGRP) in the parabrachial nucleus represent aversive information from diverse sensory modalities and signal a general alarm to the forebrain. All of the studies commonly found that CGRP stimulation increased freezing behavior among multiple defensive behaviors. However, it is unclear whether CGRP neurons can induce adaptive defensive behaviors that are relevant to specific threat circumstances. In this study, we optogenetically activated CGRP neurons when Calca-Cre mice received one of two aversive stimuli during Pavlovian fear conditioning: 1) an electrical footshock, 2) a chasing robot which mimicked an imminent predator-like threat. Our results showed that CGRP activation elevated freezing responses after the conventional conditioning with the footshock. On the other hand, the same CGRP manipulation increased flight responses after the conditioning with the chasing robot. Thus, these results clearly indicate that CGRP neurons can coordinate multiple defensive behaviors, including both freezing and flight, in order to adaptively respond to different types of threats.