Long-Term Memory Updating Parallels Altered Awake and Sleep Hippocampal Replays

The activity of hippocampal place cells is essential for various processes of spatial memory, including encoding, consolidation, and retrieval. However, whether they also participate in spatial memory updating remains elusive. This study demonstrates that during the process of long-term spatial associative memory updating, triggered by changes in reward magnitudes in a maze over consecutive days, there is a distinct period characterized by loss of preference for different reward magnitudes before adapting to new magnitude ratios. During this period, sequential replays in the hippocampus during post-training sleep are significantly biased toward the region associated with the larger reward. Additionally, replays between trials show elevated predictive power for the upcoming choices. Our results suggest that hippocampal replays may play a key role in updating long-term spatial associative memory.