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...
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eLife Sciences Publications Ltd
2025-01-01
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Online Access: | https://elifesciences.org/articles/101523 |
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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 |
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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 |
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