A novelty-retrieval-extinction paradigm leads to persistent attenuation of remote fear memories

Abstract Exposure to a novel environment can enhance the extinction of recent contextual fear in mice. This has been explained by a tagging and capture hypothesis. Consistently, we show in mice that exposure to a novel environment before extinction training promoted the extinction of recent auditory...

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Autores principales: Fulian Huang, Guangjing Zou, Can Li, Hui Meng, Xiaoyan Liu, Zehua Yang
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2020
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Acceso en línea:https://doaj.org/article/4f94635df6564eb0a6359afbae1e6e0f
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Sumario:Abstract Exposure to a novel environment can enhance the extinction of recent contextual fear in mice. This has been explained by a tagging and capture hypothesis. Consistently, we show in mice that exposure to a novel environment before extinction training promoted the extinction of recent auditory fear. However, such a promoting effect of novelty was absent for remote memories. In the present study, we replaced the regular extinction training with a retrieval-extinction session which capitalized on a reconsolidation window. When novelty exposure was followed by a retrieval-extinction session, remote fear was distinguished more easily and permanently. We have termed it as a “novelty-retrieval-extinction” paradigm. This paradigm played a greater role in the extinction of remote fear when fear conditioning and retrieval-extinction occurred in two different contexts other than in one identical context. The mechanism underlying the facilitating effect of this paradigm might involve up-regulation of histone acetylation in the hippocampus, which has been reported to increase functional and structural neuroplasticity. The present work proposes an effective, drug-free paradigm for the extinction of remote fear, which could be easily adapted in humans with least side effects.