Project Grant R01MH140966

This $659,846 Project Grant, awarded by the National Institute of Mental Health (NIMH) under the Mental Health Research Grants program (CFDA 93.242), supports a five-year research initiative at Penn State University (April 1, 2026 through January 31, 2031) investigating the epigenetic mechanisms underlying stress-enhanced fear learning in male and female mice. The research focuses on histone deacetylase 3 (HDAC3) and histone acetylation as key molecular regulators in the amygdala that mediate how acute stress predisposes individuals to excessive fear responses in post-traumatic stress disorder (PTSD). The project addresses a critical gap in understanding sex-specific differences in PTSD susceptibility, given that women are nearly twice as likely as men to develop the disorder.

The funded research delivers scientific investigation outputs across three primary aims designed to systematically characterize HDAC3's role in stress-enhanced fear learning through bidirectional manipulation of the protein during varying stress conditions in both male and female animal models. The study employs behavioral testing, molecular analysis of histone acetylation patterns, and chromatin accessibility assessments to establish how acute stress creates epigenetic molecular memory that enhances subsequent fear conditioning responses. Findings from this basic neuroscience research are expected to generate novel mechanistic insights into sex-differentiated stress vulnerability that could inform development of targeted PTSD prevention and treatment strategies.