The Intermediate CA1 and CA3 Subfields of the Hippocampus Differentially Encode Social Recognition

Abstract

Social recognition requires linking information about others to the spatial contexts in which they are encountered, a computation thought to engage the hippocampus. Although this process depends on coordinated activity across the hippocampal network, how specific subfields differentially contribute to social recognition remains unclear. Of particular interest are the intermediate CA1 (iCA1) and CA3 (iCA3) subfields, which have both been shown to be causally involved in social recognition. Historically, the dense feed-forward projections from CA3 to CA1 led to the view that these subfields form a hierarchical circuit, with CA1 primarily integrating and refining computations from CA3. However, recent causal manipulations of the iCA1 and iCA3 have revealed distinct and separable contributions to approach and avoidance behavior, suggesting functional specialization across the subfields. This functional divergence raises the possibility that iCA1 and iCA3 might differentially encode social recognition information. To test this possibility, we performed one-photon calcium imaging in freely behaving mice to record endogenous activity from the iCA1 and iCA3 during a novel behavioral paradigm that disentangles social identity from spatial position. Notably, we found that iCA3 neurons more robustly discriminated between novel and familiar conspecifics, while iCA1 neurons more strongly encoded spatial position. These results identify the iCA3 as a key locus for social novelty encoding and suggest a functional division of labor within the hippocampus, in which stable spatial frameworks in the iCA1 anchor flexible, context-dependent social representations in the iCA3 that support adaptive social memory.