The medial prefrontal cortex and the dorsomedial striatum are necessary for working memory in rats: role of NMDA receptors

Abstract

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.