Opposing roles for striatonigral and striatopallidal neurons in dorsolateral striatum in consolidating new instrumental actions

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dc.contributor.authorSmith, Alexander C. W.en
dc.contributor.authorJonkman, Sietseen
dc.contributor.authorDiFeliceantonio, Alexandra G.en
dc.contributor.authorO'Connor, Richard M.en
dc.contributor.authorGhoshal, Sohamen
dc.contributor.authorRomano, Michael F.en
dc.contributor.authorEveritt, Barry J.en
dc.contributor.authorKenny, Paul J.en
dc.date.accessioned2022-04-04T17:44:37Zen
dc.date.available2022-04-04T17:44:37Zen
dc.date.issued2021-08-25en
dc.description.abstractComparatively 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.en
dc.description.notesWe thank Denise Cai and Tristan Shuman for help with assembly of miniscopes and advice on in vivo calcium imaging. Light-sheet microscopy was performed at the Microscopy CoRE at the Icahn School of Medicine at Mount Sinai; we thank CoRE staff for training and technical support. Figures were created using BioRender.com. This work was funded by grants from the National Institutes of Health (DA043315 and DA007135 to A.C.W.S.; DA025983 to P.J.K.), the Brain and Behavior Research Foundation (NARSAD Young and Distinguished Investigator Grants to A.C.W.S. and P.J.K., respectively), iTHRIV Scholars Program (A.G.D.), and a Pfizer Postdoctoral Fellowship Award (R.M.O'C.).en
dc.description.sponsorshipNational Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [DA043315, DA007135, DA025983]; Brain and Behavior Research Foundation (NARSAD Young and Distinguished Investigator Grants); Pfizer Postdoctoral Fellowship Awarden
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41467-021-25460-3en
dc.identifier.issn2041-1723en
dc.identifier.issue1en
dc.identifier.other5121en
dc.identifier.pmid34433818en
dc.identifier.urihttp://hdl.handle.net/10919/109530en
dc.identifier.volume12en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleOpposing roles for striatonigral and striatopallidal neurons in dorsolateral striatum in consolidating new instrumental actionsen
dc.title.serialNature Communicationsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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