Epigenetic mechanisms in memory formation

Abstract

Formation of memories of events in our lives is one of the principal functions of the brain. We make particularly strong memories of events with an emotional impact. Glucocorticoid hormones, secreted in response to the stressful event, have been identified as playing an important role in the acquisition and consolidation of such memories. In recent years, significant advances have been made in the identification of the signaling and epigenomic mechanisms in the hippocampus underlying memory formation. Evidence has been accumulating for a principal role of the NMDA-ERK MAPK signaling pathway and its downstream effector molecules MSK1 and Elk-1. Activation of this signaling cascade results in the phosphorylation, acetylation, and possibly methylation of histone molecules within the chromatin structure and in the induction of immediate-early (e.g., c-Fos) and many other genes required for the molecular and cellular adaptation of the affected neurons. Glucocorticoid hormones via the glucocorticoid receptor (GR) enhance memory formation through facilitation of ERK MAPK signaling to the chromatin leading to the enhancement of epigenomic mechanisms and cognitive performance. Thus, formation of strong memories of emotional events involves an interaction between the GR and the NMDA/ERK/MSK1 and Elk-1 signaling pathways resulting in optimization of epigenomic changes in hippocampal neurons to allow the induction of required neuroplasticity changes. © Springer-Verlag Berlin Heidelberg 2011.