An epigenetic mechanism for over-consolidation of fear memories.

Autor: Barchiesi R; Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, S-581 85, Linköping, Sweden., Chanthongdee K; Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, S-581 85, Linköping, Sweden.; Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Petrella M; Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, S-581 85, Linköping, Sweden., Xu L; Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, S-581 85, Linköping, Sweden., Söderholm S; Wallenberg Centre for Molecular Medicine, Linköping University, Linköping, Sweden.; Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology; Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden., Domi E; Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, S-581 85, Linköping, Sweden., Augier G; Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, S-581 85, Linköping, Sweden., Coppola A; Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, S-581 85, Linköping, Sweden., Wiskerke J; Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, S-581 85, Linköping, Sweden., Szczot I; Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, S-581 85, Linköping, Sweden., Domi A; Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Adermark L; Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Augier E; Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, S-581 85, Linköping, Sweden., Cantù C; Wallenberg Centre for Molecular Medicine, Linköping University, Linköping, Sweden.; Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology; Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden., Heilig M; Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, S-581 85, Linköping, Sweden., Barbier E; Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, S-581 85, Linköping, Sweden. estelle.barbier@liu.se.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2022 Dec; Vol. 27 (12), pp. 4893-4904. Date of Electronic Publication: 2022 Sep 21.
DOI: 10.1038/s41380-022-01758-6
Abstrakt: Excessive fear is a hallmark of anxiety disorders, a major cause of disease burden worldwide. Substantial evidence supports a role of prefrontal cortex-amygdala circuits in the regulation of fear and anxiety, but the molecular mechanisms that regulate their activity remain poorly understood. Here, we show that downregulation of the histone methyltransferase PRDM2 in the dorsomedial prefrontal cortex enhances fear expression by modulating fear memory consolidation. We further show that Prdm2 knock-down (KD) in neurons that project from the dorsomedial prefrontal cortex to the basolateral amygdala (dmPFC-BLA) promotes increased fear expression. Prdm2 KD in the dmPFC-BLA circuit also resulted in increased expression of genes involved in synaptogenesis, suggesting that Prdm2 KD modulates consolidation of conditioned fear by modifying synaptic strength at dmPFC-BLA projection targets. Consistent with an enhanced synaptic efficacy, we found that dmPFC Prdm2 KD increased glutamatergic release probability in the BLA and increased the activity of BLA neurons in response to fear-associated cues. Together, our findings provide a new molecular mechanism for excessive fear responses, wherein PRDM2 modulates the dmPFC -BLA circuit through specific transcriptomic changes.
(© 2022. The Author(s).)
Databáze: MEDLINE
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