Long-term memories in dorsomedial and dorsolateral striatal areas differentially affect behavioral flexibility

Pauli, Wolfgang M.

Graduate Thesis Or Dissertation

Long-term memories in dorsomedial and dorsolateral striatal areas differentially affect behavioral flexibility Public Deposited

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Citeable URL: https://scholar.colorado.edu/concern/graduate_thesis_or_dissertations/2v23vt515

Abstract

Actions can be performed because they are expected to be rewarded, or simply because they have been expressed so many times that contextual cues elicit them automatically. Existing data suggest that the dorsomedial striatum (DMS) supports expectancy-driven behaviors, and that the dorsolateral striatum (DLS) allows contextual cues to elicit habitual behavior. However, it is still an open question whether or not the separable contributions of these neural substrates depend on a long-term memory of task-relevant information. Alternatively, this information may be stored in other areas that are interacting with these striatal regions. In order to address this question, rats were trained to press two levers associated with concurrent variable interval schedules of reinforcement. We ﬁrst demonstrated that injecting the NMDA antagonist DL-AP5 in the DMS during testing renders rats insensitive to contingency changes, but when injected into the DLS, it enhanced their sensitivity to contingency changes, thereby implicating their differential in expectancy-driven and habitual responding. We then used the protein kinase zeta (PKMζ) inhibitor zeta pseudosubstrate inhibitory peptide (ZIP) to determine if these regions provide storage support for the information needed to respond to contingency changes. Injecting ZIP into the DLS enhanced the rats' ability to adapt to the contingency shift, whereas injecting ZIP into the DMS had the opposite effect. It was possible to rescue the sensitivity to contingency changes by preventing the effect of ZIP with infusions of GluR23Y into the DMS one hour before ZIP microinfusions. This indicates that ZIP was preventing the ability of PKMζ to maintain established memories in the dorsal striatum by regulating GluR2-dependent AMPA receptor trafﬁcking. These results indicate that the two dorsal striatal areas actively maintain long-term memories that affect the sensitivity to contingency changes.

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