PROJECT SUMMARY Early life adversity can reprogram the developing brain and endocrine system with consequences for behavior. However, only some individuals are vulnerable to early adversity, whereas others are resilient. The differential sensitivity hypothesis proposes that resilient and vulnerable individuals differ in their degree of developmental plasticity. The goal of the proposed research is to test how three factors contribute to differences among individuals in developmental plasticity: (1) prior environmental conditions, (2) physiological reactivity to stress, and (3) glucocorticoid receptor concentrations. The proposed studies will be conducted in a captive population of zebra finches (Taeniopygia guttata), for which there is extensive evidence of programming effects of the early life environment. In combination, the results will determine whether: (1) prior experience with adversity increases vulnerability or resilience to subsequent stressors, (2) individuals that are weakly behaviorally and physiologically reactive to adversity early in life are also less reactive to stressors later in life and maintain low levels of plasticity across the lifespan and (3) hormone receptor concentrations across tissues contribute to the capacity for plasticity. We will test the effect of prior experience with adversity on subsequent responsiveness to adversity by experimentally manipulating the social environment during the postnatal period, and then testing behavioral responsiveness to social disruption during the adolescent period. We will test the relationship between physiological and behavioral reactivity to adversity by simultaneously quantifying behavior and the production of stress hormones and inflammatory cytokines after social disruption. Second, we will test the direct involvement of stress hormones and inflammatory cytokines in behavioral plasticity by experimentally manipulating hormone and cytokine levels. Finally, we will quantify receptor concentrations centrally and peripherally in individuals differing in levels of behavioral and physiological plasticity to identify glucocorticoid receptor-mediated mechanisms of plasticity. The proposed research addresses the goals of the R15 AREA program by providing novel insight into how adversity affects developmental trajectories and plasticity across the lifespan. The research will directly involve undergraduate students in hypothesis-driven research addressing biomedically relevant questions, and will enhance the research environment by providing financial support for students recruited from diverse populations to participate in research and gain experience designing, conducting, analyzing, and presenting their own experiments.