PMID- 36127428
OWN - NLM
STAT- MEDLINE
DCOM- 20221221
LR  - 20230412
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Print)
IS  - 1359-4184 (Linking)
VI  - 27
IP  - 12
DP  - 2022 Dec
TI  - An epigenetic mechanism for over-consolidation of fear memories.
PG  - 4893-4904
LID - 10.1038/s41380-022-01758-6 [doi]
AB  - 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.
CI  - (c) 2022. The Author(s).
FAU - Barchiesi, Riccardo
AU  - Barchiesi R
AUID- ORCID: 0000-0002-0514-2628
AD  - Center for Social and Affective Neuroscience, Department of Biomedical and 
      Clinical Sciences, Linkoping University, S-581 85, Linkoping, Sweden.
FAU - Chanthongdee, Kanat
AU  - Chanthongdee K
AUID- ORCID: 0000-0002-2407-9329
AD  - Center for Social and Affective Neuroscience, Department of Biomedical and 
      Clinical Sciences, Linkoping University, S-581 85, Linkoping, Sweden.
AD  - Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol 
      University, Bangkok, Thailand.
FAU - Petrella, Michele
AU  - Petrella M
AUID- ORCID: 0000-0002-5909-7527
AD  - Center for Social and Affective Neuroscience, Department of Biomedical and 
      Clinical Sciences, Linkoping University, S-581 85, Linkoping, Sweden.
FAU - Xu, Li
AU  - Xu L
AD  - Center for Social and Affective Neuroscience, Department of Biomedical and 
      Clinical Sciences, Linkoping University, S-581 85, Linkoping, Sweden.
FAU - Soderholm, Simon
AU  - Soderholm S
AUID- ORCID: 0000-0001-5350-7102
AD  - Wallenberg Centre for Molecular Medicine, Linkoping University, Linkoping, 
      Sweden.
AD  - Department of Biomedical and Clinical Sciences, Division of Molecular Medicine 
      and Virology; Faculty of Medicine and Health Sciences, Linkoping University, 
      Linkoping, Sweden.
FAU - Domi, Esi
AU  - Domi E
AUID- ORCID: 0000-0001-5726-4814
AD  - Center for Social and Affective Neuroscience, Department of Biomedical and 
      Clinical Sciences, Linkoping University, S-581 85, Linkoping, Sweden.
FAU - Augier, Gaelle
AU  - Augier G
AD  - Center for Social and Affective Neuroscience, Department of Biomedical and 
      Clinical Sciences, Linkoping University, S-581 85, Linkoping, Sweden.
FAU - Coppola, Andrea
AU  - Coppola A
AD  - Center for Social and Affective Neuroscience, Department of Biomedical and 
      Clinical Sciences, Linkoping University, S-581 85, Linkoping, Sweden.
FAU - Wiskerke, Joost
AU  - Wiskerke J
AD  - Center for Social and Affective Neuroscience, Department of Biomedical and 
      Clinical Sciences, Linkoping University, S-581 85, Linkoping, Sweden.
FAU - Szczot, Ilona
AU  - Szczot I
AD  - Center for Social and Affective Neuroscience, Department of Biomedical and 
      Clinical Sciences, Linkoping University, S-581 85, Linkoping, Sweden.
FAU - Domi, Ana
AU  - Domi A
AUID- ORCID: 0000-0003-2796-2333
AD  - Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of 
      Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 
      Gothenburg, Sweden.
FAU - Adermark, Louise
AU  - Adermark L
AUID- ORCID: 0000-0002-7165-9908
AD  - Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of 
      Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 
      Gothenburg, Sweden.
FAU - Augier, Eric
AU  - Augier E
AUID- ORCID: 0000-0002-5615-2973
AD  - Center for Social and Affective Neuroscience, Department of Biomedical and 
      Clinical Sciences, Linkoping University, S-581 85, Linkoping, Sweden.
FAU - Cantu, Claudio
AU  - Cantu C
AUID- ORCID: 0000-0003-1547-5415
AD  - Wallenberg Centre for Molecular Medicine, Linkoping University, Linkoping, 
      Sweden.
AD  - Department of Biomedical and Clinical Sciences, Division of Molecular Medicine 
      and Virology; Faculty of Medicine and Health Sciences, Linkoping University, 
      Linkoping, Sweden.
FAU - Heilig, Markus
AU  - Heilig M
AUID- ORCID: 0000-0003-2706-2482
AD  - Center for Social and Affective Neuroscience, Department of Biomedical and 
      Clinical Sciences, Linkoping University, S-581 85, Linkoping, Sweden.
FAU - Barbier, Estelle
AU  - Barbier E
AUID- ORCID: 0000-0001-6924-1855
AD  - Center for Social and Affective Neuroscience, Department of Biomedical and 
      Clinical Sciences, Linkoping University, S-581 85, Linkoping, Sweden. 
      estelle.barbier@liu.se.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220921
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
SB  - IM
EIN - Mol Psychiatry. 2022 Nov 1;:. PMID: 36319842
MH  - *Amygdala/physiology
MH  - *Basolateral Nuclear Complex/physiology
MH  - Prefrontal Cortex/metabolism
MH  - Fear/physiology
MH  - Epigenesis, Genetic
PMC - PMC9763112
COIS- The authors declare no competing interests.
EDAT- 2022/09/21 06:00
MHDA- 2022/12/22 06:00
PMCR- 2022/09/21
CRDT- 2022/09/20 23:27
PHST- 2021/12/17 00:00 [received]
PHST- 2022/08/18 00:00 [accepted]
PHST- 2022/08/09 00:00 [revised]
PHST- 2022/09/21 06:00 [pubmed]
PHST- 2022/12/22 06:00 [medline]
PHST- 2022/09/20 23:27 [entrez]
PHST- 2022/09/21 00:00 [pmc-release]
AID - 10.1038/s41380-022-01758-6 [pii]
AID - 1758 [pii]
AID - 10.1038/s41380-022-01758-6 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2022 Dec;27(12):4893-4904. doi: 10.1038/s41380-022-01758-6. Epub 
      2022 Sep 21.