Subspace communication in the hippocampal-retrosplenial axis

Abstract The capacity and flexibility of hippocampal circuits for transforming inputs into downstream outputs is fundamental for navigation and memory, yet the circuit-level mechanisms that allow this operation to adapt across experiences remain unknown. We approach this problem by performing large-scale (up to 1024-channel) recordings across the hippocampal–retrosplenial cortex (RSC) circuit in behaving mice, enabling simultaneous access to spiking activity in dentate gyrus (DG), CA3, CA2, CA1, RSC. Based on a linear dimensionality reduction technique known as partial canonical correlation analysis, we identify low-dimensional communication subspaces1 between two regions while accounting for measured third-area influences. These subspaces captured distinct input–output transformations in CA1, linking upstream (DG, CA3, and CA2) hippocampal activity to downstream cortical targets (RSC). Iintrinsic firing properties and anatomical location constrained subspace memberships—members were mapped to deep sublayers of the CA3-CA1-RSC axis during both spatial and non-spatial tasks. These subspaces could recombine overlapping neuronal pools to support distinct interareal interactions across changing experiences and brain states. Reactivation patterns of CA1-CA3 subspaces, but not those of CA1-RSC, during post-experience sleep correlated with replay, reflecting a plasticity-stability balance of the input-output transformation in the hippocampal-retrosplenial axis. Our data suggest a model in which hippocampal-neocortical communication reconfigures predetermined circuit motifs to flexibly encode experiences. Competing Interest Statement The authors have declared no competing interest.