Epigenetic Basis of Memory

The acquisition of new experiences by learning and the temporary or permanent storage of the acquired information in memory are fundamental cognitive functions essential for survival. At a cellular level, they depend on proper communication between neurons and on dynamic structural changes and synaptic reorganization. At the molecular level, this involves complex molecular signaling in the cytoplasm and nucleus of neurons (but also of glial cells). The activated cascades of signaling events drive not only the cellular and behavioral response to the received stimuli, but also contribute to fixate the learning experience into a memory trace (Kandel et al., 2014). The conversion of a learning experience into long-term memory trace requires regulated gene expression and protein synthesis. Transcriptional regulators such as CREB, Egr1, Zif268 have been identified as key factors for memory formation and storage and have been extensively studied (Alberini, 2009). But in early 2000s, the burgeoning discipline of epigenetics opened novel perspectives for the field of learning and memory, and for the first time, memory was proposed to depend on epigenetic mechanisms. In the memory field, epigenetics was initially defined as“ a mechanism for the stable maintenance of gene expression that involves physically ‘marking’ DNA or its associated proteins, without changes in underlying DNA sequences”( Levenson and Sweatt, 2005). Two reasons make epigenetic mechanisms attractive candidates as molecular substrates of memory. First, epigenetic modifications of the chromatin, like other transcriptional regulators, exert a direct control on gene expression. Further, epigenetics promises an integrative molecular framework on how environmental signals, such as learning, are dynamically integrated into the genetic landscape of an organism and may serve as molecular mnemonics that determine future behavior. Based on these hypotheses, the nature and role of epigenetic processes in learning and memory have been extensively investigated in the past decade. The ensemble of the data collected so far demonstrates that epigenetic mechanisms are engaged as integral molecular components of memory formation and are particularly important for long-term memory. This chapter summarizes the major findings from a decade of research in the field. It describes the major epigenetic modifications that have been studied and their contribution to learning and memory, in particular memory persistence. Some of the challenges in the field and outstanding questions for the years to come are also discussed

DNA Methyltransferase Inhibitors: Development and Applications

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