Effects of novelty and temporal distance on post-experience spike patterns of hippocampal place cells encoding multiple environments

The hippocampus plays a crucial role in consolidating episodic memories from diverse experiences that encompass spatial, temporal, and novel information. This study analyzed the spike patterns of hippocampal place cells in the CA3 and CA1 areas of male rats that sequentially foraged in five rooms, including familiar and novel rooms, followed by a rest period. Across the five rooms, both CA3 and CA1 place cells showed overlapping spatial representations. In a post-experience rest period, both CA3 and CA1 place cells increased baseline spike rates depending on the temporal distance from when the cells had place fields. In addition, CA3 place cells that encoded novel environments showed stronger sharp wave ripple reactivation. Coordinated reactivation of CA1 place cell ensembles that encoded temporally distant environments was eliminated. These results suggest that, following sequential experiences in multiple environments, increases in sharp wave ripple-induced spikes of hippocampal neurons more specifically process novelty-related aspects of memory, while global increases in baseline spike rates process temporal distance-related aspects. Significance Statement This study investigated how the hippocampus processes and stores memories from a series of experiences in different environments. While rats experienced familiar and novel rooms, both CA3 and CA1 neurons exhibited overlapping maps. In a post-experience rest period, these place cells increased baseline spike rates depending on the temporal distance from when the cells had place fields, suggesting processing of temporal distance-related aspects of memory. In addition, CA3 place cells that encoded novel environments specifically showed stronger reactivation during sharp wave ripples, suggesting processing of novelty-related aspects. These differential activation patterns reveal how the hippocampus integrates spatial, temporal, and novelty information from multiple experiences.