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科学家发现记忆重现与脑生物钟相关

  近日,日本东京大学等高校的科研人员在Nature Communications上发表了题为“Hippocampal clock regulates memory retrieval via Dopamine and PKA-induced GluA1 phosphorylation”的文章,发现记忆重现与脑生物钟相关,并在小鼠中鉴定出相关的特异性基因。

  人的认知能力在一天中是不同的,在下午晚些时候至傍晚时分,记忆重现功能会显着下降。目前尚不清楚局部脑生物钟在记忆表现中的功能作用。

  研究人员发现由昼夜节律依赖性转录因子BMAL1控制的海马时钟调节了一天中记忆重现的时间。小鼠前脑或海马体中可诱导的BMAL1负表达(dominant negative BMAL1,dnBMAL1),会干扰授时因子时间(Zeitgeber Time,ZT)8-12时海马记忆重现,该表现与dnBMAL1小鼠海马多巴胺cAMP信号的下调相关。具体包括多巴胺受体(Dopamine Receptors)D1-R和D5-R表达下降及受PKA(protein kinase A,蛋白激酶A)调控的GluA1-S845磷酸化程度降低。同时在dnBMAL1小鼠中,cAMP信号或D1/5Rs的药理激活挽救了受损记忆的重现。更为重要的是,GluA1 S845A敲入小鼠显示出与dnBMAL1小鼠相似的记忆重现缺陷。该研究将BMAL1与多巴胺受体的激活以及大脑中其他小信号分子的修饰联系起来,并证明了通过D1/5R-cAMP-PKA介导的GluA1磷酸化对海马时钟进行调控的机制。

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