Time and experience differentially affect distinct aspects of hippocampal representational drift.

ABSTRACT

Hippocampal activity is critical for spatial memory. Within a fixed, familiar environment, hippocampal codes gradually change over timescales of days to weeks-a phenomenon known as representational drift. The passage of time and the amount of experience are two factors that profoundly affect memory. However, thus far, it has remained unclear to what extent these factors drive hippocampal representational drift. Here, we longitudinally recorded large populations of hippocampal neurons in mice while they repeatedly explored two different familiar environments that they visited at different time intervals over weeks. We found that time and experience differentially affected distinct aspects of representational drift the passage of time drove changes in neuronal activity rates, whereas experience drove changes in the cells' spatial tuning. Changes in spatial tuning were context specific and largely independent of changes in activity rates. Thus, our results suggest that representational drift is a multi-faceted process governed by distinct neuronal mechanisms.