Inhibiting PKMζ reveals dorsal lateral and dorsal medial striatum store the different memories needed to support adaptive behavior

Learn Mem. 2012 Jun 20;19(7):307-14. doi: 10.1101/lm.025148.111.


Evidence suggests that two regions of the striatum contribute differential support to instrumental response selection. The dorsomedial striatum (DMS) is thought to support expectancy-mediated actions, and the dorsolateral striatum (DLS) is thought to support habits. Currently it is unclear whether these regions store task-relevant information or just coordinate the learning and retention of these solutions by other brain regions. To address this issue, we developed a two-lever concurrent variable-interval reinforcement operant conditioning task and used it to assess the trained rat's sensitivity to contingency shifts. Consistent with the view that these two regions make different contributions to actions and habits, injecting the NMDA antagonist DL-AP5 into the DMS just prior to the shift impaired the rat's performance but enhanced performance when injected into the DLS. To determine if these regions support memory content, we first trained rats on a biased concurrent schedule (Lever 1: VI 40" and Lever 2: VI 10"). With the intent of "erasing" the memory content stored in striatum, after this training we inhibited the putative memory-maintenance protein kinase C isozyme protein kinase Mζ (PKMζ). Infusing zeta inhibitory peptide (ZIP) into the DLS enhanced the rat's ability to adapt to the contingency shift 2 d later, whereas injecting it into the DMS had the opposite effect. Infusing GluR2(3Y) into the DMS 1 h before ZIP infusions prevented ZIP from impairing the rat's sensitivity to the contingency shift. These results support the hypothesis that the DMS stores information needed to support actions and the DLS stores information needed to support habits.

MeSH terms

  • Adaptation, Psychological / drug effects
  • Adaptation, Psychological / physiology*
  • Animals
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology
  • Corpus Striatum / anatomy & histology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / enzymology*
  • Enzyme Inhibitors / metabolism
  • Excitatory Amino Acid Antagonists / pharmacology
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology
  • Gene Expression Regulation, Enzymologic / drug effects
  • Long-Term Potentiation / drug effects
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Peptides / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • RNA, Messenger
  • Rats
  • Rats, Long-Evans
  • Receptors, AMPA / antagonists & inhibitors
  • Reinforcement, Psychology
  • Time Factors
  • Valine / analogs & derivatives
  • Valine / pharmacology


  • Enzyme Inhibitors
  • Excitatory Amino Acid Antagonists
  • Peptides
  • RNA, Messenger
  • Receptors, AMPA
  • 2-amino-5-phosphopentanoic acid
  • Protein Kinase C
  • protein kinase M zeta, rat
  • Valine
  • glutamate receptor ionotropic, AMPA 2