Organization of hippocampal CA3 into correlated cell assemblies supports a stable spatial code

Hippocampal subfield CA3 is thought to stably store memories in assemblies of recurrently connected cells functioning as a collective. However, the collective hippocampal coding properties that are unique to CA3 and how such properties facilitate the stability or precision of the neural code remain unclear. Here, we per-formed large-scale Ca2+ imaging in hippocampal CA1 and CA3 of freely behaving mice that repeatedly explored the same, initially novel environments over weeks. CA3 place cells have more precise and more stable tuning and show a higher statistical dependence with their peers compared with CA1 place cells, uncovering a cell assembly organization in CA3. Surprisingly, although tuning precision and long-term stability are correlated, cells with stronger peer dependence exhibit higher stability but not higher precision. Overall, our results expose the three-way relationship between tuning precision, long-term stability, and peer dependence, suggesting that a cell assembly organization underlies long-term storage of information in the hippocampus.

Automated summary

Hippocampal subfield CA3 is known for its role in stable memory storage. This study used large-scale Ca2+ imaging in freely behaving mice to investigate the unique coding properties of CA3 and how they contribute to the stability and precision of neural coding. The results revealed that CA3 place cells have higher precision and stability, as well as stronger statistical dependence with their peers compared to CA1 place cells, indicating a cell assembly organization in CA3. Interestingly, cells with stronger peer dependence exhibited higher stability but not higher precision. These findings highlight the relationship between tuning precision, long-term stability, and peer dependence in the hippocampus.