Smith, Alexander C. W.Jonkman, SietseDiFeliceantonio, Alexandra G.O'Connor, Richard M.Ghoshal, SohamRomano, Michael F.Everitt, Barry J.Kenny, Paul J.2022-04-042022-04-042021-08-252041-17235121http://hdl.handle.net/10919/109530Comparatively little is known about how new instrumental actions are encoded in the brain. Using whole-brain c-Fos mapping, we show that neural activity is increased in the anterior dorsolateral striatum (aDLS) of mice that successfully learn a new lever-press response to earn food rewards. Post-learning chemogenetic inhibition of aDLS disrupts consolidation of the new instrumental response. Similarly, post-learning infusion of the protein synthesis inhibitor anisomycin into the aDLS disrupts consolidation of the new response. Activity of D1 receptor-expressing medium spiny neurons (D1-MSNs) increases and D2-MSNs activity decreases in the aDLS during consolidation. Chemogenetic inhibition of D1-MSNs in aDLS disrupts the consolidation process whereas D2-MSN inhibition strengthens consolidation but blocks the expression of previously learned habit-like responses. These findings suggest that D1-MSNs in the aDLS encode new instrumental actions whereas D2-MSNs oppose this new learning and instead promote expression of habitual actions. New instrumental learning occurs through an unexpected delivery of a rewarding stimulus or the withdrawal of a punishing stimulus. The authors show that D1 receptor-expressing medium spiny neurons (MSNs) in the anterior dorsolateral striatum encode newly learned instrumental actions whereas D2 MSNs promote the expression of habitual actions.application/pdfenCreative Commons Attribution 4.0 InternationalArticle - Refereedhttps://doi.org/10.1038/s41467-021-25460-312134433818