Project Summary/Abstract Our long-term objective is to understand how neural circuits in orbitofrontal cortex (OFC) support adaptive choice behavior and produce choice biases, particularly those pertinent to drug abuse disorders. Our central hypothesis is that distinct OFC output neuron types encode unique decision variables and contribute to specific choice biases. This project has two main goals: to map the OFC neurons projecting to subcortical areas and then to study their role in decision-making by monitoring and manipulating their activity. In Aim 1, we will examine whether functional clusters of OFC neurons correspond to specific decision-making processes and whether their representations are stable over time and across different tasks. In Aim 2, we will comprehensively map OFC subcortical projections, and test if neurons projecting different regions are anatomically and molecularly distinct. Then we will focus on OFC projection neurons to the ventral striatum and the ventral tegmental area and use projection-targeted miniscope imaging to identify their roles in decision-making algorithms. In Aim 3, we will manipulate these projections to test whether they mediate specific choice biases based on past outcomes and reward size, respectively. Upon completing these aims, we expect to provide a blueprint for how decision variables are computed within the OFC and transmitted to its subcortical targets in a projection-specific manner and drive different choice biases.