The medial prefrontal cortex and the dorsomedial striatum are necessary for working memory in rats: role of NMDA receptors
Davies, Don 1985-
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Working memory is a form of short-term memory involved in the storage (maintenance) of information over time and reorganization (manipulation) of a memory set necessary for complex cognition. The human frontal cortex and striatum are involved with working memory; however, the mechanisms through which these structures contribute to working memory are incompletely understood. Given the similarities between cortical and striatal areas in the human and rodent brain, I used rats to elucidate the contrbutions of N-methyl-D-aspartate (NMDA) receptors in medial prefrontal cortex (mPFC) and dorsomedial striatum (dmSTR) using two working memory tasks. The trial unique non-match to location (TUNL) task is a delayed-non-match-to-sample visual working memory task performed in touchscreen equipped operant conditioning chambers. TUNL enables the concurrent assessment of delay-dependent and “pattern separation” effects that were not possible with previous delayed-non-match-to-sample-tasks. The odour span task (OST) measures working memory capacity using an incremental delayed-non-match-to-sample paradigm that involves the addition of stimuli (scented bowls) after each correct response. Results obtained following systemic treatment of rats with a broad spectrum NMDA receptor antagonist showed that NMDA receptors contribute to performance of both tasks. Given the contribution of cortical GluN2B-containing NMDA receptors to working memory in primates, we tested the role of these receptors in the TUNL task and OST. Systemic injections of the GluN2B-containing NMDA receptor antagonist Ro 25-6981 impaired OST but not TUNL accuracy. Additional experiments with intracranial infusions showed NMDA receptors in mPFC or dmSTR contribute to TUNL task accuracy. Ro 25-6981 infusions into dmSTR, but not mPFC impaired OST. These experiments contribute to our understanding of the role NMDA receptors perform in mPFC and dmSTR in working memory.
DegreeDoctor of Philosophy (Ph.D.)
CommitteeMulligan, Sean; Campanucci, Veronica; Borowsky, Ron
Copyright DateNovember 2016