Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA 92697-3800, USA.
Mamm Genome. 2009 Sep-Oct;20(9-10):612-23. doi: 10.1007/s00335-009-9224-3. Epub 2009 Sep 30.
An increasing body of evidence shows that structural modifications of chromatin, the DNA-protein complex that packages genomic DNA, do not only participate in maintaining cellular memory (e.g., cell fate), but they may also underlie the strengthening and maintenance of synaptic connections required for long-term changes in behavior. Accordingly, epigenetics has become a central topic in several neurobiology fields such as memory, drug addiction, and several psychiatric and mental disorders. This interest is justified as dynamic chromatin modifications may provide not only transient but also stable (or even potentially permanent) epigenetic marks to facilitate, maintain, or block transcriptional processes, which in turn may participate in the molecular neural adaptations underlying behavioral changes. Through epigenetic mechanisms the genome may be indexed in response to environmental signals, resulting in specific neural modifications that largely determine the future behavior of an organism. In this review we discuss recent advances in our understanding of how epigenetic mechanisms contribute to the formation of long-term memory and drug-seeking behavior and potentially how to apply that knowledge to the extinction of memory and drug-seeking behavior.
越来越多的证据表明,染色质的结构修饰——即包装基因组 DNA 的 DNA-蛋白质复合物——不仅参与维持细胞记忆(例如细胞命运),而且可能是行为长期变化所必需的突触连接增强和维持的基础。因此,表观遗传学已成为记忆、药物成瘾和几种精神障碍和精神疾病等几个神经生物学领域的核心课题。这种兴趣是合理的,因为动态染色质修饰不仅可以提供短暂的,还可以提供稳定的(甚至可能是永久性的)表观遗传标记,以促进、维持或阻断转录过程,而这些过程反过来又可能参与行为变化的分子神经适应。通过表观遗传机制,基因组可能会对环境信号做出反应,从而产生特定的神经修饰,这些修饰在很大程度上决定了生物体未来的行为。在这篇综述中,我们讨论了我们对表观遗传机制如何有助于形成长期记忆和觅药行为的理解的最新进展,以及如何将这些知识应用于记忆和觅药行为的消除。