Medial prefrontal cortex is a crucial node of a rapid learning system that retrieves recent and remote memories

•We studied the role of mPFC in inhibitory avoidance (IA) memory processing.•mPFC is necessary to IA memory acquisition and consolidation.•mPFC is necessary to IA memory retrieval of both recent and remote memories. The neocortex is thought to be a distributed learning system that gradually integrates semantic information into the initial mnemonic representation rapidly formed by the hippocampus after acquisition. Nevertheless, an emerging view suggests that some cortical regions, in particular the medial prefrontal cortex (mPFC), may also have a role during the initial steps of memory consolidation as well as in the recall of recent memories. Here, we show that mPFC plays a critical role during the first few hours of inhibitory avoidance memory consolidation and is necessary for the normal retrieval of both recent and remote memories, supporting the idea that involvement of neocortical areas in memory processing is not restricted to the late post-training consolidation phase.