Lateral Entorhinal Cortex Suppresses Drift in Cortical Memory Representations.

Memory retrieval is thought to depend on the reinstatement of cortical memory representations guided by pattern completion processes in the hippocampus. The lateral entorhinal cortex (LEC) is one of the intermediary regions supporting hippocampal-cortical interactions and houses neurons that prospectively signal past events in a familiar environment. To investigate the functional relevance of the activity of the LEC for cortical reinstatement, we pharmacologically inhibited the LEC and examined its impact on the stability of ensemble firing patterns in one of the efferent targets of the LEC, the medial prefrontal cortex (mPFC). When male rats underwent multiple epochs of identical stimulus sequences in the same environment, the mPFC maintained a stable ensemble firing pattern across repetitions, particularly when the sequence included pairings of neutral and aversive stimuli. With LEC inhibition, the mPFC still formed an ensemble pattern that accurately captured stimuli and their associations within each epoch. However, LEC inhibition markedly disrupted its consistency across the epochs by decreasing the proportion of mPFC neurons that stably maintained firing selectivity for stimulus associations. Thus, the LEC stabilizes cortical representations of learned stimulus associations, thereby facilitating the recovery of the original memory trace without generating a new, redundant trace for familiar experiences. Failure of this process might underlie retrieval deficits in conditions associated with degeneration of the LEC, such as normal aging and Alzheimer's disease.