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.
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.
|Nainar, Sarah; Marshall, Paul R; Tyler, Christina R et al. (2016) Evolving insights into RNA modifications and their functional diversity in the brain. Nat Neurosci 19:1292-8|
|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|