Although epigenetic regulation of gene expression has been shown to be associated with experience- dependent neural plasticity and memory formation, due to technical and conceptual limitations, the full repertoire of DNA base modifications and their role in neuropsychiatric disease remains equivocal. In this project, new technology will be developed to more precisely identify activity-dependent epigenetic mechanisms in neuronal populations selectively activated by learning and challenge current concepts related to the full repertoire of DNA base modifications and their role in regulating gene expression. Specifically, we will determine whether there is a causal relationship between various DNA base modifications and rapid behavioral adaptation, and we will advance the state of knowledge regarding the molecular mechanisms underlying the memory in a preclinical model of fear-related anxiety disorder.

Public Health Relevance

By developing new technology to simultaneously identify and characterize the role of experience-dependent modification of DNA in the regulation of gene expression underlying the formation fear-related memories in a preclinical model of neuropsychiatric disorder, the findings of the experiments outlined in this application will open up entirely new directions for research in cognitive neuroepigenetics, and may have broad translational implications by establishing novel epigenetic targets for therapeutic intervention in fear-related anxiety disorders.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZMH1)
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Beckel-Mitchener, Andrea C
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University of California Irvine
Other Basic Sciences
Schools of Arts and Sciences
United States
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Leighton, Laura J; Zhao, Qiongyi; Li, Xiang et al. (2018) A Functional Role for the Epigenetic Regulator ING1 in Activity-induced Gene Expression in Primary Cortical Neurons. Neuroscience 369:248-260
Leighton, L J; Ke, K; Zajaczkowski, E L et al. (2018) Experience-dependent neural plasticity, learning, and memory in the era of epitranscriptomics. Genes Brain Behav 17:e12426
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Baker-Andresen, Danay; Zhao, Qiongyi; Li, Xiang et al. (2015) Persistent variations in neuronal DNA methylation following cocaine self-administration and protracted abstinence in mice. Neuroepigenetics 4:1-11