Project Abstract/Summary Both drugs of abuse and necessities for life—food, socialization, procreation—recruit the evolutionarily conserved circuitry of the basal ganglia in order to integrate contextual information and facilitate action selection. Critical to this is the acquisition of associative relations between contextual reinforcement predictors and reinforcers themselves. While the spiny projection neurons (SPNs) of the ventral striatum are known to be important integrators of sensory information and learned reward salience through dopamine input, their encoding of learned cue- to-reward behavioral sequencing remains unknown. Previous studies have fundamentally disagreed with respect to the roles of the two primary populations of SPNs (dopamine receptor D1- and D2-expressing SPNs) as they pertain to reinforcement, perhaps because they have largely relied on long-term systemic disruption of population activity rather than temporally defined activity contours. My preliminary results point to a selective role of D2-SPNs in encoding reinforcement-predictive contextual cues, which I hypothesize then give way to D1-SPN activity underlying the initiation of motor programs to acquire reinforcers. I will first characterize the subsecond dynamics of D1/D2-SPN activity during cue-directed reinforcement behavior using calcium-sensor based fluorometric techniques, and investigate the predictivity of population neural activity on behavioral performance. Then, through spatiotemporally-restricted modulation of D2-SPN activity using optogenetics, I will determine the necessary resolution of cue-locked D2- SPN activity for cue-directed behavior.