Patterns across multiple memories are identified over time

Memories are not static but continue to be processed after encoding. This is thought to allow the integration of related episodes via the identification of patterns. Although this idea lies at the heart of contemporary theories of systems consolidation, it has yet to be demonstrated experimentally. Using a modified water-maze paradigm in which platforms are drawn stochastically from a spatial distribution, we found that mice were better at matching platform distributions 30 d compared to 1 d after training. Post-training time-dependent improvements in pattern matching were associated with increased sensitivity to new platforms that conflicted with the pattern. Increased sensitivity to pattern conflict was reduced by pharmacogenetic inhibition of the medial prefrontal cortex (mPFC). These results indicate that pattern identification occurs over time, which can lead to conflicts between new information and existing knowledge that must be resolved, in part, by computations carried out in the mPFC.