Epigenetics of memory and plasticity.
Although all neurons carry the same genetic information, they vary considerably in morphology and functions and respond differently to environmental conditions. Such variability results mostly from differences in gene expression. Among the processes that regulate gene activity, epigenetic mechanisms play a key role and provide an additional layer of complexity to the genome. They allow the dynamic modulation of gene expression in a locus- and cell-specific manner. These mechanisms primarily involve DNA methylation, posttranslational modifications (PTMs) of histones and noncoding RNAs that together remodel chromatin and facilitate or suppress gene expression. Through these mechanisms, the brain gains high plasticity in response to experience and can integrate and store new information to shape future neuronal and behavioral responses. Dynamic epigenetic footprints underlying the plasticity of brain cells and circuits contribute to the persistent impact of life experiences on an individual's behavior and physiology ranging from the formation of long-term memory to the sequelae of traumatic events or of drug addiction. They also contribute to the way lifestyle, life events, or exposure to environmental toxins can predispose an individual to disease. This chapter describes the most prominent examples of epigenetic marks associated with long-lasting changes in the brain induced by experience. It discusses the role of epigenetic processes in behavioral plasticity triggered by environmental experiences. A particular focus is placed on learning and memory where the importance of epigenetic modifications in brain circuits is best understood. The relevance of epigenetics in memory disorders such as dementia and Alzheimer's disease is also addressed, and promising perspectives for potential epigenetic drug treatment discussed.
Brain Research Institute, Medical Faculty of the University of Zürich, and Department of Health Sciences and Technology, Swiss Federal Institute of Technology, Brain Research Institute Zürich, Switzerland.
Bisrat T
BT
Woldemichael
Brain Research Institute, Medical Faculty of the University of Zürich, and Department of Health Sciences and Technology, Swiss Federal Institute of Technology, Brain Research Institute Zürich, Switzerland.
Johannes
J
Bohacek
Brain Research Institute, Medical Faculty of the University of Zürich, and Department of Health Sciences and Technology, Swiss Federal Institute of Technology, Brain Research Institute Zürich, Switzerland.
Katharina
K
Gapp
Brain Research Institute, Medical Faculty of the University of Zürich, and Department of Health Sciences and Technology, Swiss Federal Institute of Technology, Brain Research Institute Zürich, Switzerland.
Isabelle M
IM
Mansuy
D000818:Animals; D044127:Epigenesis, Genetic / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D008568:Memory / Q000502:physiology*; D009473:Neuronal Plasticity / Q000235:genetics*
Alzheimer's disease; Brain plasticity; DNA methylation; Early life stress; Epigenetics; Hippocampus; Histone posttranslational modifications; Learning and memory; Maternal care