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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH105398-02
Application #
8927068
Study Section
Special Emphasis Panel (ZMH1-ERB-R (02))
Program Officer
Beckel-Mitchener, Andrea C
Project Start
2014-09-15
Project End
2017-05-31
Budget Start
2015-08-01
Budget End
2016-05-31
Support Year
2
Fiscal Year
2015
Total Cost
$299,588
Indirect Cost
$99,588
Name
University of California Irvine
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
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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
Ratnu, Vikram S; Emami, Michael R; Bredy, Timothy W (2017) Genetic and epigenetic factors underlying sex differences in the regulation of gene expression in the brain. J Neurosci Res 95:301-310
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
Marshall, Paul; Bredy, Timothy W (2016) Cognitive neuroepigenetics: the next evolution in our understanding of the molecular mechanisms underlying learning and memory? NPJ Sci Learn 1:
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