The prefrontal cortex is known to be involved in a variety of functions including attention, strategy switching, response selection, task sequencing, and working memory. However, the prefrontal cortex is also involved in long term memory. The fact that prefrontal damage does not generally result in amnesia, as medial temporal lobe damage does, suggests that the prefrontal cortex is not a long term storage site for memory nor does it seem to be involved in encoding new memories like the hippocampus.
Recently, we have been investigating the hypothesis that the medial prefrontal cortex modulates (enhances or suppresses) memory retrieval in order to prevent interference. We have found that in complex multi-stimulus memory tasks, mPFC inactivation impairs acquisition of new memories and retrieval of previously acquired memories (Fig. 1). Rats with inactivation are also impaired in a proactive interference task and memory impairments are worse when there is greater potential for interference (Fig. 2).
Figure 1.
Rats were given bilateral infusions of muscimol or saline into the mPFC and trained on a complex multi-stimulus olfactory discrimination task. Muscimol rats (red bars) were significantly impaired when acquiring new memories, retrieving previously learned memories and were more susceptible to proactive interference than controls (blue bars). For more details see Peters et al., 2013.
Figure 2.
Rats were given bilateral infusions of muscimol or saline into the mPFC and trained on a continuous matching to sample task that was designed to allow us to manipulate the level of interference. We found that rats with mPFC inactivation were significantly more impaired under conditions of high interference, as compared to low interference conditions. For more details see Peters & Smith, 2020.
Peters, G. J., & Smith, D. M. (2020). The medial prefrontal cortex is needed for resolving interference even when there are no changes in task rules and strategies. Behavioral Neuroscience, 134(1), 15-20. https://doi.org/10.1037/bne0000347 
Wu, J. Q., Peters, G. J., Rittner, P., Cleland, T. A., & Smith, D. M. (2014). The hippocampus, medial prefrontal cortex, and selective memory retrieval: Evidence from a rodent model of the retrieval-induced forgetting effect. Hippocampus, 24(9), 1070–1080. https://doi.org/10.1002/hipo.22291
Peters, G. J., David, C. N., Marcus, M. D., & Smith, D. M. (2013). The medial prefrontal cortex is critical for memory retrieval and resolving interference. Learning & Memory, 20(4), 201–209. https://doi.org/10.1101/lm.029249.112 Journal Cover Art