Defining the Role of D1 and D2 Medium Spiny Neurons in the Nucleus Accumbens in Alcohol Self-Administration

Abstract ID 99086 Poster Board 130 The nucleus accumbens (NAc) is a key site of alcohol-induced dysregulation; however, contextualizing what these changes mean for behavioral control requires a deep understanding of the information encoded within the cell-type specific activity signatures in relation to behavior. The major output neurons within the NAc are medium spiny neurons (MSNs), which are segregated based on the expression of D1 or D2 dopamine receptors. These cells make up 95% of the cells in this population and are nearly non-overlapping. Work has hypothesized that D1 and D2 MSNs have opposing valence-based roles in behavior; however, here we show that these cells do not show opposing activity patterns and neither D1 nor D2 MSN population signals reward or valence. To address this question, the genetically encoded calcium sensor, GCaMP6f was expressed in D1 and D2 MSNs via Cre-dependent viral expression in D1- and A2a-cre mice, respectively. The temporal dynamics of each population were recorded using fiber photometry during a range of Pavlovian and operant conditioning tasks where behavior is controlled by appetitive (sucrose, alcohol) and aversive (footshock) stimuli. Neural responses were isolated around behaviorally relevant events such as in response to discriminative cues, operant responses, appetitive stimuli, aversive stimuli, and alcohol drinking bouts. Across all of these tasks, D1 MSN responses tracked salience, and were evoked by sensory stimuli, footshock, sucrose and scaled with intensity. D2 MSNs responses were evoked by both cues and the predicted outcomes, dynamically changed with learning, and tracked valence-free prediction error. Furthermore, we find these cell populations also signal properties of alcohol drinking during operant alcohol self-administration which drives alcohol reinforcement. Integrating these findings with our understanding of alcohol use disorder, we try to understand how value-based learning contributes to the development and maintenance of alcohol use disorder.