Parabrachial CGRP neurons modulate active defensive behavior under a naturalistic threat
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.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.
Article and author information
Author details
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
© 2025, Pyeon et al.
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.
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