Stress peptides sensitize fear circuitry to promote passive coping.

Autor: Pliota P; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Dr. Bohr Gasse 7, 1030, Vienna, Austria., Böhm V; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Dr. Bohr Gasse 7, 1030, Vienna, Austria., Grössl F; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Dr. Bohr Gasse 7, 1030, Vienna, Austria., Griessner J; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Dr. Bohr Gasse 7, 1030, Vienna, Austria., Valenti O; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Dr. Bohr Gasse 7, 1030, Vienna, Austria.; Division of Neurophysiology and Neuropharmacology, Centre for Physiology and Pharmacology, Medical Univ. Vienna, Schwarzspanierstrasse 17, 1090, Vienna, Austria., Kraitsy K; Preclinical Phenotyping, Vienna Biocenter (VBC), Dr. Bohr Gasse 3, 1030, Vienna, Austria., Kaczanowska J; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Dr. Bohr Gasse 7, 1030, Vienna, Austria., Pasieka M; Bioinformatics and Scientific Computing, Vienna Biocenter (VBC), Dr. Bohr Gasse 3, 1030, Vienna, Austria., Lendl T; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Dr. Bohr Gasse 7, 1030, Vienna, Austria., Deussing JM; Department of Stress Neurobiology & Neurogenetics, Max Planck Institute of Psychiatry, 80804, Munich, Germany., Haubensak W; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Dr. Bohr Gasse 7, 1030, Vienna, Austria. wulf.haubensak@imp.ac.at.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2020 Feb; Vol. 25 (2), pp. 428-441. Date of Electronic Publication: 2018 Jun 14.
DOI: 10.1038/s41380-018-0089-2
Abstrakt: Survival relies on optimizing behavioral responses through experience. Animals often react to acute stress by switching to passive behavioral responses when coping with environmental challenge. Despite recent advances in dissecting mammalian circuitry for Pavlovian fear, the neuronal basis underlying this form of non-Pavlovian anxiety-related behavioral plasticity remains poorly understood. Here, we report that aversive experience recruits the posterior paraventricular thalamus (PVT) and corticotropin-releasing hormone (CRH) and sensitizes a Pavlovian fear circuit to promote passive responding. Site-specific lesions and optogenetic manipulations reveal that PVT-to-central amygdala (CE) projections activate anxiogenic neuronal populations in the CE that release local CRH in response to acute stress. CRH potentiates basolateral (BLA)-CE connectivity and antagonizes inhibitory gating of CE output, a mechanism linked to Pavlovian fear, to facilitate the switch from active to passive behavior. Thus, PVT-amygdala fear circuitry uses inhibitory gating in the CE as a shared dynamic motif, but relies on different cellular mechanisms (postsynaptic long-term potentiation vs. presynaptic facilitation), to multiplex active/passive response bias in Pavlovian and non-Pavlovian behavioral plasticity. These results establish a framework promoting stress-induced passive responding, which might contribute to passive emotional coping seen in human fear- and anxiety-related disorders.
Databáze: MEDLINE
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