Heyward Frankie D, Sweatt J David
Department of Neurobiology, Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Neurobiology, Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL, USA
Neuroscientist. 2015 Oct;21(5):475-89. doi: 10.1177/1073858415579635. Epub 2015 Apr 1.
The establishment of synaptic plasticity and long-term memory requires lasting cellular and molecular modifications that, as a whole, must endure despite the rapid turnover of their constituent parts. Such a molecular feat must be mediated by a stable, self-perpetuating, cellular information storage mechanism. DNA methylation, being the archetypal cellular information storage mechanism, has been heavily implicated as being necessary for stable activity-dependent transcriptional alterations within the CNS. This review details the foundational discoveries from both gene-targeted and whole-genome sequencing studies that have brought DNA methylation to our attention as a chief regulator of activity- and experience-dependent transcriptional alterations within the CNS. We present a hypothetical framework to resolve disparate experimental findings regarding distinct manipulations of DNA methylation and their effect on memory, taking into account the unique impact activity-dependent alterations in DNA methylation potentially have on both memory-promoting and memory-suppressing gene expression. And last, we discuss potential avenues for future inquiry into the role of DNA methylation during remote memory formation.
突触可塑性和长期记忆的建立需要持久的细胞和分子修饰，总体而言，尽管其组成部分快速更新，但这些修饰必须持续存在。这样的分子壮举必定由一种稳定、自我延续的细胞信息存储机制介导。DNA甲基化作为典型的细胞信息存储机制，已被强烈认为是中枢神经系统内稳定的活动依赖性转录改变所必需的。本综述详细介绍了来自基因靶向和全基因组测序研究的基础发现，这些发现使我们将DNA甲基化视为中枢神经系统内活动和经验依赖性转录改变的主要调节因子。我们提出了一个假设框架，以解决关于DNA甲基化的不同操作及其对记忆的影响的不同实验结果，同时考虑到DNA甲基化的活动依赖性改变可能对促进记忆和抑制记忆的基因表达产生的独特影响。最后，我们讨论了未来探究DNA甲基化在远程记忆形成过程中作用的潜在途径。
