PROJECT SUMMARY ? ANIMAL MODELS CORE The Animal Models Core provides a broad range of the most sophisticated mouse models of depression and acute behavioral assays to support the Center's goals to establish epigenetic mechanisms of depression and other stress-related disorders. Such models include several chronic stress paradigms in adult mice as well as paradigms of early life stress, with a focus on comparisons of stress responses in male and female animals across the life cycle. The imperative to employ this broad behavioral battery is that it is difficult to infer something about such a heterogeneous syndrome as depression, about which there is still limited etiologic and pathophysiological information, from a single model or even a limited number of models. The Core then utilizes these models in two main ways. First, the Core provides microdissections of limbic brain regions from carefully defined mouse models for molecular characterization in all four Projects and in the Chromatin and Gene Analysis Core. Second, the Core provides extensive behavioral characterization after manipulation of specific genes of interest to Projects 1 through 4 and is, consequently, instrumental in providing causal, mechanistic data on how specific forms of epigenetic regulation, and the specific target genes affected, influence depression-related behaviors. The Core accomplishes this by analyzing a range of genetic mutant mice as well as by utilizing intra-cerebral injection of viral vectors or of small molecule activators/inhibitors of target proteins. Additionally, the Core is responsible for generating most of the viral vectors used by Project investigators. The Core also collaborates with each of the Projects to employ neurophysiological recording techniques, optogenetic tools, and fiber photometry with in vivo calcium imaging to understanding how stress-induced gene regulation controls the functioning of the affected neurons and their circuits to cause behavioral abnormalities. By consolidating this behavioral, viral vector, and functional work within a centralized Core, we ensure rigorous control over the data and facilitate comparisons and contrasts of experimental results across the individual Projects. This consolidation also makes financial sense, since we concentrate and maximize efficient use of our complementary expertise.