Interactions between medial prefrontal cortex and dorsomedial striatum are necessary for odor span capacity in rats: role of GluN2B-containing NMDA receptors

Working memory is involved in the maintenance and manipulation of information essential for complex cognition. While the neural substrates underlying working memory capacity have been studied in humans, considerably less is known about the circuitry mediating working memory capacity in rodents. Therefore, the present experiments tested the involvement of medial prefrontal cortex (mPFC) and dorsal striatum (STR) in the odor span task (OST), a task proposed to assay working memory capacity in rodents. Initially, Long Evans rats were trained to dig in scented sand for food following a serial delayed nonmatching-to-sample rule. Temporary inactivation of dorsomedial (dm) STR significantly reduced span in well trained rats. Inactivation of mPFC or contralateral disconnection of the mPFC and dmSTR also reduced span. Infusing the GluN2B-containing NMDA receptor antagonist Ro 25-6981 into mPFC did not affect span; however, span was significantly reduced following bilateral Ro 25-6981 infusions into dmSTR or contralateral disconnection of mPFC (inactivation) and dmSTR (Ro 25-6981). These results suggest that span capacity in rats depends on GluN2B-containing NMDA receptor-dependent interactions between the mPFC and the dmSTR. Therefore, interventions targeting this circuit may improve the working memory capacity impairments in patients with schizophrenia, Alzheimer's disease, and Parkinson's disease.