Epigenetic regulation of memory formation and maintenance

Abstract

Understanding the cellular and molecular mechanisms underlying the formation and maintenance of memories is a central goal of the neuroscience community. It is well regarded that an organism's ability to lastingly adapt its behavior in response to a transient environmental stimulus relies on the central nervous system's capability for structural and functional plasticity. This plasticity is dependent on a well-regulated program of neurotransmitter release, post-synaptic receptor activation, intracellular signaling cascades, gene transcription, and subsequent protein synthesis. In the last decade, epigenetic markers like DNA methylation and post-translational modifications of histone tails have emerged as important regulators of the memory process. Their ability to regulate gene transcription dynamically in response to neuronal activation supports the consolidation of long-term memory. Furthermore, the persistent and self-propagating nature of these mechanisms, particularly DNA methylation, suggests a molecular mechanism for memory maintenance. In this review, we will examine the evidence that supports a role of epigenetic mechanisms in learning and memory. In doing so, we hope to emphasize (1) the widespread involvement of these mechanisms across different behavioral paradigms and distinct brain regions, (2) the temporal and genetic specificity of these mechanisms in response to upstream signaling cascades, and (3) the functional outcome these mechanisms may have on structural and functional plasticity. Finally, we consider the future directions of neuroepigenetic research as it relates to neuronal storage of information.

Inhibition of different histone acetyltransferases (HATs) uncovers transcription-dependent and -independent acetylation-mediated mechanisms in memory formation

“…Remodeling of chromatin is mediated by DNA methylation and post-translational modifications of histones. In particular, the reversible and dynamic acetylation on the amino-terminal tails of histones has been identified as critical regulator of transcriptional processes in neuronal plasticity and memory formation (Sharma 2010;Lubin et al 2011;Zovkic et al 2013). Acetylation is mediated by histone acetyltransferases (HATs), and is reversed by histone deacetylases (HDACs) (Selvi et al 2010;Haggarty and Tsai 2011).…”

“…The vast majority of work deals with acetylation in LTM processes (Sharma 2010;Lubin et al 2011;Zovkic et al 2013). Interestingly, manipulation of acetylation-dependent processes by the HAT inhibitor garcinol also affects transient memory in honeybees (Merschbaecher et al 2012).…”

Implementing Test Enhanced Learning: Swedish Teacher Students’ Perception of Quizzing

“…For the intended learning to occur, the to-be-learned-information needs to be mentally processed; i.e. fundamentally, be preserved, or formed to a memory (Zovkic, Guzman-Karlsson, & Sweatt, 2013). Simply put, as memories are formed, learning takes place.…”

Epigenetic programming of the neuroendocrine stress response by adult life stress

“…Although miRNAs do not alter chromatin structure and therefore technically do not follow the classical definition of epigenetics, they are, more often than not, considered important players in the epigenetic control of posttranscriptional gene expression. Altogether, these epigenetic modifications constitute important mechanisms by which transient environmental stimuli can induce persistent changes in gene expression and ultimately behaviour (Zovkic et al 2013). However, the exact consequences of epigenetic modifications for gene transcription are not that straight forward, but seem to be context dependent and determined by both the location and the nature of the modification.…”