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In episodic memory, the spatial location or context in which an event takes place is thought to be encoded by hippocampal place cells. However, whether the place cells that are associated with a memory are reactivated during memory retrieval is unknown. Ji and colleagues now reveal that, in rats, CA1 place cells that encode the location of an aversive experience are reactivated during retrieval of the memory of that event.

The authors recorded rat CA1 place cells while the animals explored a linear track, of which one half was lit and the other half was in darkness. On day 1, the rats explored the track for two ∼10-minute sessions, which were separated by a rest. The next day, the rats explored the track in more sessions; during the second session, the rats were foot-shocked twice while at the far end of the dark half of the track — the 'shock zone'.

ripple-associated replays can encode stored, although not necessarily intended, trajectories

On day 1 and in the pre-shock session on day 2, the rats showed a mild preference for the dark half of the track. By contrast, in the post-shock session, the animals actively avoided the shock zone, often pausing before turning away from this region. During these pauses, place cells fired in sequences encoding a trajectory from the animal's current position to the shock zone, even though the animal had not entered this zone. Notably, this 'replay' was associated with increased high-frequency ripple activity. These findings indicate that ripple-associated replays can encode stored, although not necessarily intended, trajectories.

Interestingly, in the post-shock session, an animal was more likely to move away from the shock zone if it had a replay that ended with the firing of a place cell with a place field in this zone than if the replay ended with the firing of a place cell with a field corresponding to elsewhere on the track. Moreover, compared with replay-encoded trajectories during the pre-shock session or day 1 sessions, replay-encoded trajectories during the post-shock session showed reduced overlap with the animal's subsequent physical trajectories. Thus, rats actively avoided following the trajectories encoded by replay events in the post-shock session.

Together, these findings suggest that awake replay of place cell sequences occurs during retrieval of encoded trajectories and is crucial for the planning of future behaviour.