Numerous human psychopathologies, including post-traumatic stress, anxiety, and affective disorders are characterized by the dysregulation of emotional processing mechanisms, yet the biological events which regulate individual susceptibility to these conditions are unknown. In addition to genetic and environmental factors, recent evidence suggests that epigenetic events, a class of genomic modifications that are not encoded in the DNA, may contribute to normal emotional learning and may be a source of abnormality in emotional pathology. Work from the LeDoux laboratory has recently shown that Pavlovian cued fear conditioning, a well-established model for the study of """"""""normal"""""""" fear circuitry in the amygdala can also be used to identify atypical or extreme fear reactivity phenotypes. Using this behavioral paradigm, in combination with molecular techniques, the primary goal of this project will be to assess epigenetic modifications in the amygdala that predict extreme individual differences in fear reactivity phenotypes. To accomplish this goal, I will first use a standard protocol to identify individuals manifesting outlier emotional traits. I will then apply a combination of Western immunoblotting and chromatin immunoprecipitation to identify individual differences in specific histone modifications. Finally, I will investigate the effect of pharmacologically modulating histone acetylation on fear phenotypes.
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| Hoeffer, Charles A; Cowansage, Kiriana K; Arnold, Elizabeth C et al. (2011) Inhibition of the interactions between eukaryotic initiation factors 4E and 4G impairs long-term associative memory consolidation but not reconsolidation. Proc Natl Acad Sci U S A 108:3383-8 |
| Monfils, Marie-H; Cowansage, Kiriana K; Klann, Eric et al. (2009) Extinction-reconsolidation boundaries: key to persistent attenuation of fear memories. Science 324:951-5 |
