Prefrontal–hippocampal interaction during the encoding of new memories

The hippocampus rapidly forms associations among ongoing events as they unfold and later instructs the gradual stabilisation of their memory traces in the neocortex. Although this two-stage model of memory consolidation has gained substantial empirical support, parallel evidence from rodent studies suggests that the neocortex, in particular the medial prefrontal cortex, might work in concert with the hippocampus during the encoding of new experiences. This opinion article first summarises findings from behavioural, electrophysiological, and molecular studies in rodents that uncovered immediate changes in synaptic connectivity and neural selectivity in the medial prefrontal cortex during and shortly after novel experiences. Based on these findings, I then propose a model positing that the medial prefrontal cortex and hippocampus might use different strategies to encode information during novel experiences, leading to the parallel formation of complementary memory traces in the two regions. The hippocampus captures moment-to-moment changes in incoming inputs with accurate spatial and temporal contexts, whereas the medial prefrontal cortex may sort the inputs based on their similarity and integrates them over time. These processes of pattern recognition and integration enable the medial prefrontal cortex to, in real time, capture the central content of novel experience and emit relevancy signal that helps to enhance the contrast between the relevant and incidental features of the experience. This hypothesis serves as a framework for future investigations on the potential top-down modulation that the medial prefrontal cortex may exert over the hippocampus to enable the selective, perhaps more intelligent encoding of new information.