Walters B J, Zovkic I B
The Hospital for Sick Children, Department of Neuroscience and Mental Health, Toronto, ON, Canada.
University of Toronto Mississauga, Department of Psychology, Mississauga, ON, Canada.
Neuroscience. 2015 Aug 6;300:39-52. doi: 10.1016/j.neuroscience.2015.05.005. Epub 2015 May 9.
Memory formation is a protracted process in which recently acquired events are consolidated to produce stable and specific associations. Initially, newly acquired information undergoes cellular consolidation in the hippocampus, which transiently supports the storage of recently acquired memories. In contrast, remote, or "old" memories are maintained in the cortex and show almost complete independence from the hippocampus. Memories are transferred from the hippocampus to the cortex through a process termed systems consolidation. Emerging evidence suggests that recurrent activation, or "training" of the cortex by the hippocampus is vital to systems consolidation. This process involves prolonged waves of memory-related gene activity in the hippocampus and cortex long after the learning event has terminated. Indeed, molecular events occurring within hours and days of fear conditioning are essential for stabilizing and eventually transitioning the memory to the cortex. It is increasingly evident that molecular mechanisms that exhibit a capacity for prolonged activation may underlie systems consolidation. Processes that have the capacity to control protein abundance over long time scales, such as epigenetic modifications, are prime candidates for the molecular mechanism of systems consolidation. Indeed, recent work has established two types of epigenetic modifications as integral for systems consolidation. First, localized nucleosomal histone variant exchange and histone modifications are integral for early stages of systems consolidation, whereas DNA methylation appears to be utilized to form stable marks that support memory maintenance. Since systems consolidation also requires discrete and time-sensitive changes in protein abundance, additional mechanisms, such as protein degradation, need also be considered, although their role in systems consolidation has yet to be investigated. Here, we discuss the role of molecular mechanisms in systems consolidation and their implications for understanding how memories persist over time.
记忆形成是一个漫长的过程，在此过程中，最近获取的事件被巩固以产生稳定且特定的关联。最初，新获取的信息在海马体中经历细胞巩固，海马体短暂地支持最近获取记忆的存储。相比之下，远期或“旧”记忆则保存在皮层中，并且几乎完全独立于海马体。记忆通过一个称为系统巩固的过程从海马体转移到皮层。新出现的证据表明，海马体对皮层的反复激活或“训练”对系统巩固至关重要。这个过程涉及到学习事件终止很久之后，海马体和皮层中与记忆相关的基因活动的长时间波动。事实上，恐惧条件反射数小时和数天内发生的分子事件对于稳定记忆并最终将其转移到皮层至关重要。越来越明显的是，具有长时间激活能力的分子机制可能是系统巩固的基础。能够在长时间尺度上控制蛋白质丰度的过程，如表观遗传修饰，是系统巩固分子机制的主要候选者。事实上，最近的研究已经确定了两种表观遗传修饰是系统巩固所必需的。首先，局部核小体组蛋白变体交换和组蛋白修饰是系统巩固早期阶段所必需的，而DNA甲基化似乎被用来形成支持记忆维持的稳定标记。由于系统巩固还需要蛋白质丰度的离散且对时间敏感的变化，因此还需要考虑其他机制，如蛋白质降解，尽管它们在系统巩固中的作用尚未得到研究。在这里，我们讨论分子机制在系统巩固中的作用及其对理解记忆如何随时间持续存在的意义。
