Study Maps Low-Dimensional Subspaces Linking Hippocampus and Retrosplenial Cortex

A new study published in Nature examined how the hippocampus communicates with the retrosplenial cortex during behavior in mice. Researchers used up to 1,024-channel recordings to monitor spiking activity simultaneously in the dentate gyrus, CA3, CA2, CA1, and the retrosplenial cortex.

The team applied partial canonical correlation analysis to isolate low-dimensional communication subspaces between pairs of regions while controlling for activity in a third area. These subspaces captured distinct input-output transformations that link upstream hippocampal activity to downstream cortical targets.

Intrinsic firing properties and anatomical location constrained which neurons participated in each subspace. Members were concentrated in deep sublayers of the CA3-CA1-RSC axis and appeared during both spatial and non-spatial tasks.

Subspaces could recombine overlapping neuronal pools to support different inter-regional interactions as experiences and brain states changed. Cross-regional subspaces adapted to different environments, and subspace members preserved maze-related manifold geometry better than non-members.

Reactivation patterns of CA1-CA3 subspaces during post-experience sleep correlated with replay and spike correlations, while CA1-RSC subspace reactivation did not show the same relationship. The findings suggest hippocampal-neocortical communication reconfigures predetermined circuit motifs to encode experiences flexibly.