White André O, Wood Marcelo A
University of California, Irvine, Department of Neurobiology & Behavior, Irvine, CA, United States; Center for the Neurobiology of Learning & Memory, Irvine, CA, United States.
University of California, Irvine, Department of Neurobiology & Behavior, Irvine, CA, United States; Center for the Neurobiology of Learning & Memory, Irvine, CA, United States.
Neurobiol Learn Mem. 2014 Jul;112:61-7. doi: 10.1016/j.nlm.2013.10.007. Epub 2013 Oct 19.
It has been known for numerous decades that gene expression is required for long-lasting forms of memory. In the past decade, the study of epigenetic mechanisms in memory processes has revealed yet another layer of complexity in the regulation of gene expression. Epigenetic mechanisms do not only provide complexity in the protein regulatory complexes that control coordinate transcription for specific cell function, but the epigenome encodes critical information that integrates experience and cellular history for specific cell functions as well. Thus, epigenetic mechanisms provide a unique mechanism of gene expression regulation for memory processes. This may be why critical negative regulators of gene expression, such as histone deacetylases (HDACs), have powerful effects on the formation and persistence of memory. For example, HDAC inhibition has been shown to transform a subthreshold learning event into robust long-term memory and also generate a form of long-term memory that persists beyond the point at which normal long-term memory fails. A key question that is explored in this review, from a learning and memory perspective, is whether stress-dependent signaling drives the formation and persistence of long-term memory via HDAC-dependent mechanisms.
数十年来，人们已经知道基因表达是持久记忆形式所必需的。在过去十年中，对记忆过程中表观遗传机制的研究揭示了基因表达调控中又一层复杂性。表观遗传机制不仅在控制特定细胞功能的协调转录的蛋白质调节复合物中提供复杂性，而且表观基因组还编码关键信息，这些信息整合了特定细胞功能的经验和细胞历史。因此，表观遗传机制为记忆过程提供了一种独特的基因表达调控机制。这可能就是为什么基因表达的关键负调节因子，如组蛋白脱乙酰酶（HDACs），对记忆的形成和持续有强大影响的原因。例如，HDAC抑制已被证明能将阈下学习事件转化为强大的长期记忆，还能产生一种长期记忆形式，这种记忆在正常长期记忆衰退后仍能持续。从学习和记忆的角度来看，本综述探讨的一个关键问题是，应激依赖性信号是否通过HDAC依赖性机制驱动长期记忆的形成和持续。
