The medial prefrontal cortex during flexible decisions: Evidence for its role in distinct working memory processes.

During decisions that involve working memory, task-related information must be encoded, maintained across delays, and retrieved. Few studies have attempted to causally disambiguate how different brain structures contribute to each of these components of working memory. In the present study, we used transient optogenetic disruptions of rat medial prefrontal cortex (mPFC) during a serial spatial reversal learning (SSRL) task to test its role in these specific working memory processes. By analyzing numerous performance metrics, we found: (1) mPFC disruption impaired performance during only the choice epoch of initial discrimination learning of the SSRL task; (2) mPFC disruption impaired performance in dissociable ways across all task epochs (delay, choice, return) during flexible decision-making; (3) mPFC disruption resulted in a reduction of the typical vicarious-trial-and-error rate modulation that was related to changes in task demands. Taken together, these findings suggest that the mPFC plays an outsized role in working memory retrieval, becomes involved in encoding and maintenance when recent memories conflict with task demands, and enables animals to flexibly utilize working memory to update behavior as environments change.