Subspace communication in the hippocampal–retrosplenial axis
9 affiliations
- 1Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, USA
- 2Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA
- 3Department of Biomedical Engineering, New York University Tandon School of Engineering, Brooklyn, NY, USA. [email protected]
- 4Department of Neuroscience, New York University Grossman School of Medicine, New York, NY, USA. [email protected]
- 5Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, USA. [email protected]
- 6Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA. [email protected]
- 7Center for Neural Science, New York University, New York, NY, USA. [email protected]
- 8Department of Neuroscience, New York University Grossman School of Medicine, New York, NY, USA. [email protected]
- 9Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA. [email protected]
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 subspaces 1 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.
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BibTeX
@article{gonzalez2026subspace,
title = {{Subspace communication in the hippocampal–retrosplenial axis}},
author = {Joaquín González and Mihály Vöröslakos and Deren Aykan and Nina Nitzan Soto and Noam Nitzan and Rachel Swanson and Mürsel Karadas and Zhe Sage Chen and György Buzsáki},
journal = {Nature},
year = {2026},
month = may,
doi = {10.1038/s41586-026-10481-z},
url = {https://doi.org/10.1038/s41586-026-10481-z},
note = {CC BY},
}
RIS
TY - JOUR
TI - Subspace communication in the hippocampal–retrosplenial axis
AU - Joaquín González
AU - Mihály Vöröslakos
AU - Deren Aykan
AU - Nina Nitzan Soto
AU - Noam Nitzan
AU - Rachel Swanson
AU - Mürsel Karadas
AU - Zhe Sage Chen
AU - György Buzsáki
PY - 2026
DA - 2026/05/13
JO - Nature
DO - 10.1038/s41586-026-10481-z
UR - https://doi.org/10.1038/s41586-026-10481-z
AB - 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 subspaces 1 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.
SN - 0028-0836
SN - 1476-4687
ER -