Laboratorio de Neurobiología de la Memoria, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE), UBA-CONICET, Ciudad Universitaria, 1428EHA, Buenos Aires, Argentina.
Mol Neurobiol. 2019 Feb;56(2):1437-1450. doi: 10.1007/s12035-018-1144-3. Epub 2018 Jun 9.
Although important information is available on the molecular mechanisms of long-term memory formation, little is known about the processes underlying memory persistence in the brain. Here, we report that persistent gene expression of CaMKIIδ isoform participates in object recognition long-lasting memory storage in mice hippocampus. We found that CaMKIIδ mRNA expression was sustained up to one week after training and paralleled memory retention. Antisense DNA infusion in the hippocampus during consolidation or even after consolidation impairs 7-day- but not 1-day-long memory, supporting a role of CaMKIIδ in memory persistence. CaMKIIδ gene expression was accompanied by long-lasting nucleosome occupancy changes at its promoter. This epigenetic mechanism is described for the first time in a memory process and offers a novel mechanism for persistent gene expression in neurons. CaMKIIδ protein is mainly present in nucleus and presynaptic terminals, suggesting a role in these subcellular compartments for memory persistence. All these results point to a key function of the sustained gene expression of this overlooked CaMKII isoform in long-lasting memories.
尽管关于长期记忆形成的分子机制有重要信息，但关于大脑中记忆持久性的过程知之甚少。在这里，我们报告说，CaMKIIδ 同工型的持久基因表达参与了小鼠海马体的物体识别长期记忆储存。我们发现，CaMKIIδ mRNA 的表达在训练后可持续长达一周，与记忆保持时间平行。在巩固过程中甚至在巩固后向海马体输注反义 DNA 会损害 7 天但不会损害 1 天的记忆，这支持了 CaMKIIδ 在记忆持久性中的作用。CaMKIIδ 基因表达伴随着其启动子处的长时核小体占据变化。这种表观遗传机制在记忆过程中首次被描述，并为神经元中持久基因表达提供了一种新的机制。CaMKIIδ 蛋白主要存在于细胞核和突触前末端，表明其在这些亚细胞隔室中具有记忆持久性的作用。所有这些结果都表明，这种被忽视的 CaMKII 同工型的持续基因表达在长期记忆中具有关键功能。
