PROJECT SUMMARY Early life adversity (ELA), such as neglect or maltreatment in childhood, is a major risk factor for the development of psychiatric disorders later in life. ELA heightens responses to threats, usually at the expense of rewarding behaviors. Excessive threat avoidance is a hallmark of anxiety, phobias, and depression. Circuits that process both rewards and threats, including the basolateral amygdala (BLA), are known to be dysregulated by ELA and have been implicated in the pathophysiology of these conditions. These circuits mature throughout early life and into early adulthood. This extended window of development, when paired with enhanced exploration in adolescence, facilitates refinement of neural circuits underlying nuanced behavioral strategies needed throughout life. Salient experiences, such as ELA, are encoded in groups of coactive neuronal ensembles throughout the brain and have the capability to impact circuit organization. Although symptoms of psychiatric disorders often manifest in adolescence, most studies focus on adult outcomes of ELA. As a result, the biological mechanisms connecting ELA to enhanced threat avoidance later in life remain largely unknown. This proposal aims to bridge this gap by determining how ELA-sensitive cells within the BLA drive brain-wide circuit reorganization underlying enhanced avoidance behavior in adolescent mice. My central hypothesis will be tested in two aims. Experiments in Aim 1 will reveal the endogenous activity of ELA-sensitive ensembles in the BLA during threat avoidance behavior and map their brain-wide connectivity. Experiments in Aim 2 will identify sensitive windows during development when ELA-sensitive neurons alter developmental circuit trajectories, leading to increased avoidance. I will gain extensive training in the neurobiology of ELA and application of systems neuroscience approaches including activity-dependent genetic labeling, chemogenetics and whole brain circuit mapping to the developing brain. This research will illuminate how early experiences can alter the trajectory of postnatal brain development and identify sensitive windows and targets for circuit-level therapeutics that can be used to prevent or treat mental health disorders in at-risk populations.