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Learning and Long-term Memory

開催日 2014/9/13
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

CREB/CRTC plays a dual role in LTM maintenance and LTM extinction

  • P3-211
  • 中村 直介 / Naosuke Nakamura:1 齊藤 実 / Minoru Saitoe:2 平野 恭敬 / Yukinori Hirano:1 
  • 1:京都大院・医・メディカルイノベーションセンター・SKプロジェクト / SK Project, Medical Innovation Center, Grad. Sch. Med., Kyoto Univ., Kyoto, Japan 2:東京都医学総合研 / Tokyo Metropolitan Institute of Medical Science 

Memory is consolidated to a stable form of memory, long-term memory (LTM), which is mediated by CREB-dependent gene expression. Animals can retrieve LTM if consolidated LTM is properly maintained, although the underlying mechanism of LTM maintenance is currently unclear. Here we provide evidences indicating novel dual roles of CREB in LTM maintenance and extinction in olfactory memory in Drosophila. We found that CREB activity is important for, not only consolidation, but also maintenance of LTM up to 4 days after training. In contrast to LTM consolidation that requires a CREB co-activator, CBP (CREB-binding protein), but not another co-activator, CRTC (cAMP-regulated transcriptional co-activator), LTM maintenance was dependent on CRTC, but not CBP. To gain insight into the mechanism of LTM maintenance, we identified CREB/CRTC target genes by ChIP-seq analysis. Knockdown of the target genes did not affect LTM consolidation, but did impair LTM maintenance, supporting the idea that CREB/CRTC regulates genes involved in LTM maintenance. Intriguingly, after 4 days post training, CREB/CRTC was dispensable for LTM maintenance, raising a question why CREB/CRTC acts on a limited time window in LTM maintenance. We found that LTM can be extinguished during this CREB/CRTC-dependent phase of LTM maintenance, but not after 4 days post training. Activation of CRTC after 4 days post training allowed LTM to be extinguished. Taken together, we propose a novel model in which CREB/CRTC plays a dual role in LTM maintenance and LTM extinction. This dual function would allow filtering of LTM to persist or to be extinguished, which is beneficial to adapt to the environment.

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