2022-09-21 スウェーデン・リンショーピング大学
今回の研究では、多くの遺伝子の発現を抑制するエピジェネティック酵素であるPRDM2と呼ばれるタンパク質について調べた。
PRDM2の発現を低下させると、恐怖に関連した記憶の定着が促進されることを明らかにした。
研究チームは、PRDM2のレベルが低下したときに影響を受ける遺伝子も特定した。その結果、前頭葉と扁桃体をつなぐ神経細胞の活性が上昇することが明らかとなった。
<関連情報>
- https://liu.se/en/news-item/sa-fastnar-skrammande-minnen-i-vissa-hjarnor
- https://www.nature.com/articles/s41380-022-01758-6
恐怖記憶の過固定化に関するエピジェネティックなメカニズム An epigenetic mechanism for over-consolidation of fear memories
Barchiesi Riccardo,Chanthongdee Kanat,Petrella Michele,Xu Li,Söderholm Simon,Domi Esi,Augier Gaelle,Coppola Andrea,Joost Wiskerke,Ilona Szczot,Domi Ana,Adermark Louise,Augier Eric,Cantù Claudio,Heilig Markus & Barbier Estelle
Molecular Psychiatry Published:21 September 2022
DOI:https://doi.org/10.1038/s41380-022-01758-6
Abstract
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.
