Hippocampal CA1 replay becomes less prominent but more rigid without inputs from medial entorhinal cortex

The hippocampus is an essential brain area for learning and memory. However, the network mechanisms underlying memory storage, consolidation and retrieval remain incompletely understood. Place cell sequences during theta oscillations are thought to be replayed during non-theta states to support consolidation and route planning. In animals with medial entorhinal cortex (MEC) lesions, the temporal organization of theta-related hippocampal activity is disrupted, which allows us to test whether replay is also compromised. Two different analyses—comparison of co-activation patterns between running and rest epochs and analysis of the recurrence of place cell sequences—reveal that the enhancement of replay by behavior is reduced in MEC-lesioned versus control rats. In contrast, the degree of intrinsic network structure prior and subsequent to behavior remains unaffected by MEC lesions. The MEC-dependent temporal coordination during theta states therefore appears to facilitate behavior-related plasticity, but does not disrupt pre-existing functional connectivity. Medial entorhinal cortex (MEC) is involved in memory processes that entail the replay of sequential firing of hippocampal place cells during rest periods and during behaviour. Here, the authors show that MEC lesioned animals show intact replay after an epoch of rats running on a linear track, while replay during the behavioral epoch is reduced.