Theta coordinates hippocampal-entorhinal ensembles during wake and rest

Precisely timed interactions between hippocampal and cortical cells, during quiescent periods dominated by replay of CA1 cell sequences, are thought to support memory consolidation. However, the processes during encoding that lead to coordinated offline replay remain poorly understood. We found entrainment of deep-layer medial entorhinal cortex (dMEC) cells to CA1 cell assemblies dictated their later recruitment and synchronisation with hippocampal replay. These assembly-entrained cells participated preferentially in replay which included their CA1 assembly partner and in forward-projecting replay sequences. Finally, replay coordination of these dMEC cells showed a marked experience-dependent increase; becoming stronger as an animal became fluent with a novel spatial task. Together these findings suggest cell assemblies may support information propagation in hippocampo-cortical circuits and the establishment of long-term memories.