Subspace communication in the hippocampal–retrosplenial axis

The capacity of hippocampal circuits to transform inputs into downstream outputs is fundamental to navigation and memory, yet the circuit-level mechanisms that enable this flexibility in adapting to experience remain unclear. Here we approach this problem by performing large-scale (up to 1,024 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 and RSC. On the basis of a linear dimensionality-reduction technique known as partial canonical correlation analysis, we identify low-dimensional communication subspaces1 between two regions while accounting for influences from a third area. These subspaces captured distinct input–output transformations in the CA1 region, linking upstream hippocampal activity (DG, CA3 and CA2) to downstream cortical targets (RSC). Intrinsic 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 in the input–output transformation along the hippocampal–retrosplenial axis. Our findings suggest a model in which hippocampal–neocortical communication reconfigures predetermined circuit motifs to flexibly encode experiences. Hippocampal–neocortical communication reconfigures predetermined circuit motifs to flexibly encode experiences.