Epigenetic mechanisms in stress-related memory formation

Coping with stressful events is part of everyone's daily life. The organism's response to stress is a complex array of physiological and behavioral changes aimed at the preservation/protection of the organism during the stressful event as well as at stimulating adaptive and mnemonic processes in case the event would re-occur in the future. The hippocampus including its 'gate', the dentate gyrus, is highly involved in these processes. We have been collecting evidence suggesting that the transcriptional activation seen in dentate gyrus neurons, which are involved in the encoding of memories of a psychologically stressful event, requires chromatin remodeling in these neurons driven by the phosphorylation (at Serine10) and acetylation (at Lysine14) of histone H3. These particular epigenetic mechanisms are potentially of special interest for neuronal functioning as they are associated with the induction of hitherto silent genes. The phospho-acetylation of histone H3 is brought about by the concurrent activation of two, possibly converging, signaling pathways, being the glucocorticoid receptor and the NMDA/MAPK/ERK/MSK signaling pathways. Thus, we present a new model about how signaling to the chromatin can shape a specific gene transcriptional response in dentate granule neurons required for the encoding of memory of the stressful event. (c) 2007 Elsevier Ltd. All rights reserved.