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.