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Neuronal ensemble-specific DNA methylation strengthens engram stability.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-31 , DOI: 10.1038/s41467-020-14498-4 Kubra Gulmez Karaca 1, 2 , Janina Kupke 1 , David V C Brito 1 , Benjamin Zeuch 1 , Christian Thome 3 , Dieter Weichenhan 4 , Pavlo Lutsik 4 , Christoph Plass 4 , Ana M M Oliveira 1
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-31 , DOI: 10.1038/s41467-020-14498-4 Kubra Gulmez Karaca 1, 2 , Janina Kupke 1 , David V C Brito 1 , Benjamin Zeuch 1 , Christian Thome 3 , Dieter Weichenhan 4 , Pavlo Lutsik 4 , Christoph Plass 4 , Ana M M Oliveira 1
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Memories are encoded by memory traces or engrams, represented within subsets of neurons that are synchronously activated during learning. However, the molecular mechanisms that drive engram stabilization during consolidation and consequently ensure its reactivation by memory recall are not fully understood. In this study we manipulate, during memory consolidation, the levels of the de novo DNA methyltransferase 3a2 (Dnmt3a2) selectively within dentate gyrus neurons activated by fear conditioning. We found that Dnmt3a2 upregulation enhances memory performance in mice and improves the fidelity of reconstitution of the original neuronal ensemble upon memory retrieval. Moreover, similar manipulation in a sparse, non-engram subset of neurons does not bias engram allocation or modulate memory strength. We further show that neuronal Dnmt3a2 overexpression changes the DNA methylation profile of synaptic plasticity-related genes. Our data implicates DNA methylation selectively within neuronal ensembles as a mechanism of stabilizing engrams during consolidation that supports successful memory retrieval.
中文翻译：
神经元合奏特异的DNA甲基化增强了字母的稳定性。
记忆是由记忆痕迹或字母进行编码的，它们表示在学习过程中同步激活的神经元子集中。但是，尚不完全了解在巩固过程中驱动字母稳定并因此确保其通过记忆回忆被重新激活的分子机制。在这项研究中，我们在记忆巩固期间操纵由恐惧条件激活的齿状回神经元中的从头DNA甲基转移酶3a2（Dnmt3a2）的水平。我们发现，Dnmt3a2的上调增强了小鼠的记忆力，并提高了记忆检索时原始神经元集合重构的保真度。此外，在神经元的稀疏，非字母组中的类似操作不会偏向字母分配或调节记忆力。我们进一步表明，神经元Dnmt3a2过表达改变了突触可塑性相关基因的DNA甲基化谱。我们的数据暗示DNA甲基化选择性地在神经元集成体内作为巩固过程中稳定信号的机制，从而支持成功的记忆检索。
更新日期：2020-01-31
中文翻译：
神经元合奏特异的DNA甲基化增强了字母的稳定性。
记忆是由记忆痕迹或字母进行编码的，它们表示在学习过程中同步激活的神经元子集中。但是，尚不完全了解在巩固过程中驱动字母稳定并因此确保其通过记忆回忆被重新激活的分子机制。在这项研究中，我们在记忆巩固期间操纵由恐惧条件激活的齿状回神经元中的从头DNA甲基转移酶3a2（Dnmt3a2）的水平。我们发现，Dnmt3a2的上调增强了小鼠的记忆力，并提高了记忆检索时原始神经元集合重构的保真度。此外，在神经元的稀疏，非字母组中的类似操作不会偏向字母分配或调节记忆力。我们进一步表明，神经元Dnmt3a2过表达改变了突触可塑性相关基因的DNA甲基化谱。我们的数据暗示DNA甲基化选择性地在神经元集成体内作为巩固过程中稳定信号的机制，从而支持成功的记忆检索。
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