Replay of hippocampal place cell sequences has been proposed as a fundamental mechanism of learning and memory. However, the standard interpretation of replay has been challenged by reports that similar activity is observed before experience ('preplay'). By the preplay account, pre-existing temporal sequences are mapped onto new experiences without learning sequential structure. Here we employed high density recording methods to monitor hundreds of place cells simultaneously while rats explored multiple novel environments. While we observed large numbers of synchronous spiking events before experience, they were not temporally correlated with subsequent experience. Multiple measures differentiated pre-experience and postexperience events that, taken together, defined the latter but not the former as trajectory-depicting. The formation of events with these properties was prevented by administration of an NMDA-receptor antagonist during experience. These results suggest that the sequential structure of behavioral episodes is encoded during experience and reexpressed as trajectory events.
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