Hippocampal remapping induced by new behavior is mediated by spatial context

The hippocampus plays a central role in episodic memory and spatial navigation. Hippocampal neurons form unique representational codes in different spatial environments, which may provide a neural substrate for context that can trigger memory recall or enable performance of context-guided memory tasks. However, new learning often occurs in a familiar location, requiring that location’s representation to be updated without erasing the previously existing memory representations that may be adaptive again in the future. To study how new learning affects a previously acquired spatial memory representation, we trained mice to perform two plus maze tasks across nine days in the sequence Turn Right 1 – Go East – Turn Right 2 (three days each), while we used single-photon calcium imaging to record the activity of hundreds of neurons in dorsal CA1. One cohort of mice performed the entire experiment on the same maze (One-Maze), while the second cohort performed the Go East task on a unique maze (Two-Maze). We hypothesized that CA1 representations in One-Maze mice would exhibit more change in the spatial patterns of neuronal activity on the maze from Turn Right 1 to Turn Right 2 than would be seen in Two-Maze mice. Indeed, changes in single unit activity and in the population code were larger in the One-Maze group. We further show evidence that Two-Maze mice utilize a separate neural representation for each maze environment. Finally, we found that remapping across the two Turn Right epochs did not involve an erasure of the representation for the first Turn Right experience, as many neurons in mice from both groups maintained Turn Right-associated patterns of activity even after performing the Go East rule. These results demonstrate that hippocampal activity patterns remap in response to new learning, that remapping is greater when experiences occur in the same spatial context, and that throughout remapping information from each experience is preserved. Significance Statement The hippocampus plays a central role in self-localization and the consolidation of new experiences into long term memory. The activity of hippocampal place cells tracks an animal’s spatial location and upcoming navigational decisions, providing, at the ensemble level, unique patterns of activity for experiences that occur in the same physical location. Many studies have demonstrated the existence of divergent patterns at short time scales and how remapping can orthogonalize distinct experiences learned simultaneously. Here, we expand on this knowledge using the power of single-photon calcium imaging to track how new learning affects previously existing spatial memories either in the same or different environments over long periods of time. We observe patterns of hippocampal neural activity in mice during performance of two different rules either in the same environment or in different environments. We find that performing a new behavioral rule in the same environment as a previous rule causes significantly more remapping of hippocampal activity associated with the first rule than observed in mice that perform the two rules in separate environments. However, this remapping does not wholly destabilize memory for the first rule, as many neurons in both groups of mice maintain spatial activity patterns specific to the first rule. These results provide an important step forward in understanding the function of the hippocampus in memory by dramatically expanding the temporal scale over which changes to memory are measured.