SUMMARY Goal-directed actions are behaviors directed towards achieving outcomes of high value. Individuals who experience early-life adversity instead favor habit-based behaviors that are insensitive to reward value. Such insensitivity can contribute to depression and its diverse symptoms, including anhedonia and social withdrawal. A primary goal of the parent R01 is to understand the mechanisms by which social isolation disrupts goal-directed decision making. Major discoveries are: 1) social isolation in adolescence causes failures in goal-directed decision making later in life. 2) Dendritic spine plasticity (or lack thereof) on neurons within coordinated cortico-amygdala circuits causally contribute to failures in the ability of mice to select actions based on the likelihood that they will be rewarded with valued outcomes. My lab simultaneously developed tests for understanding the capacity of social experiences to modulate goal-directed actions – for example, a couple might routinely visit a particular restaurant because it is where they had their first date. Mice are trained to respond for two equally preferred food reinforcers in operant conditioning chambers. Then, one food is paired with a novel conspecific, while the other is paired with a novel object. When returned to the conditioning chambers for a probe test, mice prefer the food associated with the novel conspecific. Thus, we have in hand a procedure that quantifies the social incentivization of future choice (SIFC) in mice. Under the parent grant, the lab initially focused on orbitofrontal cortical control of action. Interestingly, though, the team found that SIFC instead requires the adjacent prelimbic prefrontal cortex (PL) and its interactions with the basolateral amygdala (BLA). For instance, inactivation of PL-to-BLA projections obstruct the ability of social interactions to confer value to external rewards. This exciting finding inspired my proposal to: (1) define the mechanisms controlling value-based action and its influence by social experiences, focusing on PL-BLA interactions. I will test the hypothesis that excitatory input onto BLA neurons from the PL triggers dendritic spine plasticity on BLA neurons, which is required for SIFC. Then, I will team with Emory collaborator Dr. Malavika Murugan to leverage in vivo cellular resolution calcium imaging and genetically encoded calcium indicators to infer what types of information neuron populations within PL-BLA circuits encode. (2) I will then determine whether social isolation during adolescence derails the ability of social experience to incentivize later goal-seeking behavior, with the hypothesis that social isolation disrupts the capacity of social interactions to later incentivize goal-directed choice. Positive outcomes now, during the initial years of my PhD training, will position me as I enter advanced training to better understand long-term consequences of social poverty and develop strategies to improve goal-se...