Epigenetic mechanisms underlying extinction of memory and drug-seeking behavior

Abstract

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.

Fig. 1

This schematic illustrates the amino terminal tails of two of the core histone proteins, histones H3 and H4, which are the sites of numerous post-translational modifications. Sites marked with a modification (Me methylation, P phosphorylation, Ac acetylation) are those that have been examined with regard to learning and memory processes and drug addiction, respectively