Parabrachial CGRP neurons modulate active defensive behavior under a naturalistic threat

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Abstract

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 neuron during robot chasing elevated flight responses in both conditioning and retention tests, presumably by amyplifying 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, ensuring adaptive responses to varying levels of danger.

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All data generated or analyzed during this study are included in the manuscript and supporting files.

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Gyeong Hee Pyeon

School of Psychology, Korea University, Seoul, Republic of Korea

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-4013-3206
Hyewon Cho

School of Psychology, Korea University, Seoul, Republic of Korea

Competing interests
The authors declare that no competing interests exist.
Byung Min Chung

School of Psychology, Korea University, Seoul, Republic of Korea

Competing interests
The authors declare that no competing interests exist.
June-Seek Choi

School of Psychology, Korea University, Seoul, Republic of Korea

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4394-2140
Yong Sang Jo

School of Psychology, Korea University, Seoul, Republic of Korea

For correspondence
ysjo@korea.ac.kr

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-7716-0964

Funding

National Research Foundation of Korea (2022M3E5E8017804)

Yong Sang Jo

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were performed during the dark phase of the cycle under the guidelines of the Institutional Animal Care and Use Committee at the Korea University (KUIACUC-2022-0057).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.