Project Summary The nucleus accumbens (NAc) plays an important role in the acquisition and expression of many stimulus- reward associations, a process which can be co-opted by drugs of abuse. Information processing in the NAc is thought to be regulated by incoming glutamatergic signals from multiple areas, but the dynamic properties of these different signals are not well understood. This project will focus on the role of three prominent inputs arising from the medial prefrontal cortex, basolateral amygdala, and ventral hippocampus. Studies have begun to reveal the role of these pathways in mediating behavior guided by both natural rewards and drugs of abuse. However, it is still largely unknown to what extent the coordination of NAc neural dynamics with each of those inputs is modulated by experience, dopaminergic signaling, or reward type. The goal of this project is to address these issues using innovative approaches that combine large-scale neural recordings, optogenetics, and reward conditioning in mice. The first aim is to use large-scale neural recordings to determine whether synchrony between the NAc and the three designated inputs is differentially modified during associative reward learning. Additionally, this aim will determine the role of midbrain dopaminergic signaling in input selection, by using transient optogenetic suppression of dopamine neuron activity to modulate synchrony between the NAc and its inputs. The second aim is to combine neural recordings and transient optogenetic suppression of individual input signals to the NAc, to deconstruct the role of specific inputs in shaping neural coding and task performance at different stages of training. The goal in the third aim is to determine how, during periods of reward abstinence, neural synchrony between the NAc and its inputs is differentially modulated by cues previously associated with cocaine or food. Together, this study will greatly advance our understanding of how reward-related information processing in the nucleus accumbens is influenced by signals from three important and functionally diverse input sources.