Parabrachial CGRP neurons modulate active defensive behavior under a naturalistic threat

Recent studies suggest that calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) represent aversive information and signal a general alarm to the forebrain. If CGRP neurons serve as a true general alarm, their activation would modulate both passive nad active defensive be...

Full description

Saved in:
Bibliographic Details
Main Authors: Gyeong Hee Pyeon, Hyewon Cho, Byung Min Chung, June-Seek Choi, Yong Sang Jo
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2025-01-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/101523
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832095928708759552
author Gyeong Hee Pyeon
Hyewon Cho
Byung Min Chung
June-Seek Choi
Yong Sang Jo
author_facet Gyeong Hee Pyeon
Hyewon Cho
Byung Min Chung
June-Seek Choi
Yong Sang Jo
author_sort Gyeong Hee Pyeon
collection DOAJ
description Recent studies suggest that calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) represent aversive information and signal a general alarm to the forebrain. If CGRP neurons serve as a true general alarm, their activation would modulate both passive nad 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.
format Article
id doaj-art-0869a7cac5af4110b530ce96dabf0ca0
institution Kabale University
issn 2050-084X
language English
publishDate 2025-01-01
publisher eLife Sciences Publications Ltd
record_format Article
series eLife
spelling doaj-art-0869a7cac5af4110b530ce96dabf0ca02025-02-05T16:22:34ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011410.7554/eLife.101523Parabrachial CGRP neurons modulate active defensive behavior under a naturalistic threatGyeong Hee Pyeon0https://orcid.org/0000-0003-4013-3206Hyewon Cho1Byung Min Chung2June-Seek Choi3https://orcid.org/0000-0002-4394-2140Yong Sang Jo4https://orcid.org/0000-0002-7716-0964School of Psychology, Korea University, Seoul, Republic of KoreaSchool of Psychology, Korea University, Seoul, Republic of KoreaSchool of Psychology, Korea University, Seoul, Republic of KoreaSchool of Psychology, Korea University, Seoul, Republic of KoreaSchool of Psychology, Korea University, Seoul, Republic of KoreaRecent studies suggest that calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) represent aversive information and signal a general alarm to the forebrain. If CGRP neurons serve as a true general alarm, their activation would modulate both passive nad 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.https://elifesciences.org/articles/101523CGRPfear conditioningfleeingfreezingparabrachial nucleusdefensive behavior
spellingShingle Gyeong Hee Pyeon
Hyewon Cho
Byung Min Chung
June-Seek Choi
Yong Sang Jo
Parabrachial CGRP neurons modulate active defensive behavior under a naturalistic threat
eLife
CGRP
fear conditioning
fleeing
freezing
parabrachial nucleus
defensive behavior
title Parabrachial CGRP neurons modulate active defensive behavior under a naturalistic threat
title_full Parabrachial CGRP neurons modulate active defensive behavior under a naturalistic threat
title_fullStr Parabrachial CGRP neurons modulate active defensive behavior under a naturalistic threat
title_full_unstemmed Parabrachial CGRP neurons modulate active defensive behavior under a naturalistic threat
title_short Parabrachial CGRP neurons modulate active defensive behavior under a naturalistic threat
title_sort parabrachial cgrp neurons modulate active defensive behavior under a naturalistic threat
topic CGRP
fear conditioning
fleeing
freezing
parabrachial nucleus
defensive behavior
url https://elifesciences.org/articles/101523
work_keys_str_mv AT gyeongheepyeon parabrachialcgrpneuronsmodulateactivedefensivebehaviorunderanaturalisticthreat
AT hyewoncho parabrachialcgrpneuronsmodulateactivedefensivebehaviorunderanaturalisticthreat
AT byungminchung parabrachialcgrpneuronsmodulateactivedefensivebehaviorunderanaturalisticthreat
AT juneseekchoi parabrachialcgrpneuronsmodulateactivedefensivebehaviorunderanaturalisticthreat
AT yongsangjo parabrachialcgrpneuronsmodulateactivedefensivebehaviorunderanaturalisticthreat