Multiplexed action-outcome representation by striatal striosome-matrix compartments detected with a novel cost-benefit foraging task

ABSTRACT Learning about positive and negative outcomes of actions is crucial for survival and underpinned by conserved circuits including the striatum. How associations between actions and outcomes are formed is not fully understood, particularly when the outcomes have mixed positive and negative features. We developed a novel foraging (‘bandit’) task requiring mice to maximize rewards while minimizing punishments. By 2-photon Ca ++ imaging, we monitored activity of 5831 identified anterodorsal striatal striosomal and matrix neurons. Surprisingly, we found that action-outcome associations for reward and punishment were combinatorially encoded rather than being integrated as overall outcome value. Single neurons could, for one action, encode outcomes of opposing valence. Striosome compartments consistently exhibited stronger representations of reinforcement outcomes than matrix, especially for high reward or punishment prediction errors. These findings demonstrate a remarkable multiplexing of action-outcome contingencies by single identified striatal neurons and suggest that striosomal neurons are differentially important in action-outcome learning.