한빛사논문
Sukjae J. Kang1,6, Jong-Hyun Kim1,5,6, Dong-Il Kim1, Benjamin Z. Roberts1,2 & Sung Han1,2,3,4
1Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
2Neuroscience Graduate Program, University of California San Diego, La Jolla, CA, USA.
3Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, Republic of Korea.
4Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Republic of Korea.
5Present address: Center for Cognition and Sociality, Institute for Basic Science, Daejeon, Republic of Korea.
6These authors contributed equally: Sukjae J. Kang, Jong-Hyun Kim.
Corresponding author : Correspondence to Sung Han.
Abstract
Panic disorder is characterized by uncontrollable fear accompanied by somatic symptoms that distinguish it from other anxiety disorders. Neural mechanisms underlying these unique symptoms are not completely understood. Here, we report that the pituitary adenylate cyclase-activating polypeptide (PACAP)-expressing neurons in the lateral parabrachial nucleus projecting to the dorsal raphe are crucial for panic-like behavioral and physiological alterations. These neurons are activated by panicogenic stimuli but inhibited in conditioned fear and anxiogenic conditions. Activating these neurons elicits strong defensive behaviors and rapid cardiorespiratory increase without creating aversive memory, whereas inhibiting them attenuates panic-associated symptoms. Chemogenetic or pharmacological inhibition of downstream PACAP receptor-expressing dorsal raphe neurons abolishes panic-like symptoms. The pontomesencephalic PACAPergic pathway is therefore a likely mediator of panicogenesis, and may be a promising therapeutic target for treating panic disorder.
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