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

Nat Commun. 2021 Aug 25;12(1):5121. doi: 10.1038/s41467-021-25460-3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Conditioning, Operant*
  • Corpus Striatum / cytology
  • Corpus Striatum / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / physiology*
  • Rats
  • Rats, Long-Evans
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism


  • Receptors, Dopamine D1
  • Receptors, Dopamine D2