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If CGRP neurons serve as a true general alarm, their activation would modulate both passive and active defensive behaviors depending on the magnitude and context of the threat. However, most prior research has focused on the role of CGRP neurons in passive freezing responses, with limited exploration of their involvement in active defensive behaviors. To address this, we examined the role of CGRP neurons in active defensive behavior using a predator-like robot programmed to chase mice. Our electrophysiological results revealed that CGRP neurons encode the intensity of aversive stimuli through variations in firing durations and amplitudes. Optogenetic activation of CGRP neurons during robot chasing elevated flight responses in both conditioning and retention tests, presumably by amplifying the perception of the threat as more imminent and dangerous. In contrast, animals with inactivated CGRP neurons exhibited reduced flight responses, even when the robot was programmed to appear highly threatening during conditioning. These findings expand the understanding of CGRP neurons in the PBN as a critical alarm system, capable of dynamically regulating active defensive behaviors by amplifying threat perception, and ensuring adaptive responses to varying levels of danger.<\/jats:p>","DOI":"10.7554\/elife.101523","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T05:30:08Z","timestamp":1736487008000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.101523","source":"Crossref","is-referenced-by-count":12,"title":["Parabrachial CGRP neurons modulate active defensive behavior under a naturalistic threat"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4013-3206","authenticated-orcid":true,"given":"Gyeong Hee","family":"Pyeon","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047dqcg40","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Psychology, Korea University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Hyewon","family":"Cho","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047dqcg40","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Psychology, Korea University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"given":"Byung Min","family":"Chung","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047dqcg40","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Psychology, Korea University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4394-2140","authenticated-orcid":true,"given":"June-Seek","family":"Choi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047dqcg40","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Psychology, Korea University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7716-0964","authenticated-orcid":true,"given":"Yong Sang","family":"Jo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047dqcg40","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Psychology, Korea University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"bib1","first-page":"841","type":"journal-article","article-title":"Convergence of nociceptive information on the parabrachio-amygdala neurons in the rat","volume":"307","author":"Bernard","year":"1988","journal-title":"Comptes Rendus de l\u2019Academie Des Sciences. 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