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

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Smith, Alexander C W  ORCID logo
Jonkman, Sietse 
Difeliceantonio, Alexandra G  ORCID logo
O'Connor, Richard M 


Comparatively 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.



Corpus Striatum, Neurons, Animals, Mice, Inbred C57BL, Mice, Rats, Rats, Long-Evans, Receptors, Dopamine D1, Receptors, Dopamine D2, Behavior, Animal, Conditioning, Operant, Male

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Nature communications

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NIDA NIH HHS (T32 DA007135, F32 DA043315, R01 DA025983)