Aversive experience drives offline ensemble reactivation to link memories across days.

Memories are encoded in neural ensembles during learning and stabilized by post-learning reactivation. Integrating recent experiences into existing memories ensures that memories contain the most recently available information, but how neural ensembles accomplish this critical process remains unknown. Here we show that in mice, a strong aversive experience drives the offline ensemble reactivation of not only the recent aversive memory but also a neutral memory formed two days prior, spreading the fear from the recent aversive memory to the previous neutral memory. We find that fear specifically spreads retrospectively, but not prospectively, to neutral memories across days. Consistent with prior studies, we find reactivation of the recent aversive memory ensemble during the offline period following learning. However, a strong aversive experience also increases co-reactivation of the aversive and neutral memory ensembles during the offline period. Finally, inhibiting hippocampal reactivation during this offline period abolishes the spread of fear from the aversive experience to the neutral memory. Taken together, these results demonstrate that strong aversive experience can drive retrospective memory integration through the offline co-reactivation of recent memory ensembles with memory ensembles formed days prior, providing a neural mechanism by which memories can be integrated across days.