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NatureNeurosciencePeer-reviewed journal article

Granule cells reorient cortical trajectories to separate contexts

Martha G. Garcia-GarciaiD, Michał J. WójcikiD, Srijan Thota, Luke DrakeiD, Amma Otchere, Oluwatobi Akinwale, Lizmaylin Ramos, Rui Ponte CostaiD, Mark J. WagneriD

PDFDOIPreprint

In-depth summary

Claude Opus 5.5 · xhigh effort · 7 Nov 2026 · from the full text of version 4 (31 Jul 2026) · CC0 1.0

In mice learning two tasks, cerebellar granule cells kept the low-rank geometry of premotor cortical output within each task but rotated their population trajectories apart between tasks, while cortex generalized.

Low-dimensional cortical manifolds aid generalization but cause interference between contexts, whereas expansion layers such as cerebellar granule cells (GrCs) are thought to separate contexts by high-dimensional projection at the cost of smooth geometry. Imaging pons-projecting premotor layer 5 pyramidal tract (L5PT) neurons and GrCs together tests this directly and finds that GrCs separate contexts by reorienting low-rank trajectories instead.

Key results

  1. ShownWithin each task, GrC activity was about as low-rank as premotor L5PT output and reproduced its representational similarity structure. GrCs did not expand cortical dynamics into a high-dimensional code.

    Participation ratio, Reach: L5PT 4.1±0.2 vs GrCs 5.0±0.5 (p=0.001); virtual-reality (VR) task: 4.3±0.3 vs 4.1±0.2 (p=0.054). Single-trial PR was lower for GrCs in both tasks (p=0.0003). L5PT-GrC representational similarity analysis (RSA): Spearman ρ=0.83±0.03 within task vs 0.41±0.2 across tasks (p=0.0003). 18 session pairs from 9 mice. · Similar L5PT and GrC representations; GrCs preserve within-task L5PT geometry; Figure legends

  2. ShownAcross tasks, single L5PT neurons and population modes generalized, while GrCs remapped in time through phase shifts and polarity inversions. L5PT-GrC communicating subspaces stayed similarly correlated in both tasks.

    Attenuation-corrected cross-task correlation, single cells: r=0.58±0.05 L5PT vs 0.23±0.1 GrCs (p=0.002). Top 2 joint-task PCs: 0.83±0.02 vs 0.24±0.1 (p=0.002). Same-task controls did not differ (p=0.3). Population modes raised L5PT consistency (0.58 to 0.83, p=0.0005) but not GrC consistency (0.23 vs 0.24, p=0.7). Canonical correlation strength was conserved across tasks (173 canonical variables, r=0.69). · L5PTs generalize but GrCs remap; Canonical Correlation Analysis (CCA); Figure legends

  3. ShownGrC remapping was coherent: trajectories rotated within the plane or elongated out of it between tasks, and the size of these changes predicted decorrelation. L5PT-to-GrC mappings and GrC state decoders did not transfer across tasks.

    Procrustes rotation 54±12° GrCs vs 19±3° L5PT (p=0.007); elongation 46±9% vs 26±5% (p=0.02); no difference in same-task controls. Rotation and elongation predicted decorrelation (adjusted R^2=0.82). L5PT-to-GrC regression: r^2=0.72±0.2 same-task vs 0.2±0.1 cross-task (p=0.008). Cross-task linear discriminant decoding of delay vs reward: 90±2% L5PT vs 68±6% GrCs (p=0.0009). · GrC trajectories reorient between tasks; L5-GrC mapping reconfigures across tasks; GrC behavioral readout remaps; Figure legends

  4. SuggestedExtra GrC cross-task separation, beyond L5PT, grew with training and was largest when mice licked predictively in both tasks, so GrC codes diverged as behaviour converged.

    ΔDecorrelation (GrC PC1 minus L5PT PC1) was modestly higher in trained than novice pairs (p=0.037; 18 trained, 9 novice). It correlated with the dual-task predictive licking score (ρ=0.6, p=0.001), and predictive pairs exceeded reactive pairs (p=0.0009, 26 pairs). Recomputed with all tracked cells, ρ=0.56. · GrC task separation grows with learning; Behavioral Analysis; Figure legends

  5. SuggestedIn a simulated mossy fiber-GrC-readout network trained on two alternating prediction tasks, a task-specific rotation of the GrC input learned faster than sparse high-rank expansion and reduced interference about as well as expansion did. A plain geometry-preserving relay suffered catastrophic forgetting.

    100 mossy fiber inputs, 100-fold GrC expansion with 4 fixed random inputs per GrC, a trained linear readout, 20 seeds. Relay and Rotation learned faster than Expansion (1/τ from exponential loss fits). Relay forgot Task 1 while training on Task 2. Tangling the Relay inputs slowed learning toward the Expansion baseline. The text gives no numerical effect sizes. · Manifold rotation for optimal learning; Model architectures; Learning speed; Figure legends

Methods, data and reproducibility

Dual-site two-photon calcium imaging of jRGECO1a-labelled pons-projecting premotor L5PT neurons and GCaMP6f-labelled GrCs while mice alternated between a robotic forelimb reach task and a virtual-reality running task sharing an action, 1-s delay, reward timeline. Tracked cells were compared by PCA, participation ratio, canonical correlation, similarity analysis and decoding; three GrC-layer models were simulated.

  • Math1-Cre×Ai93×ztTA mice expressing GCaMP6f in GrCs, with jRGECO1a in pons-projecting premotor L5PT neurons, dual-site imaged · mouse · n = 10 mice (5 male) · 10.5061/dryad.9p8cz8x0p (Dryad)
  • Trained cross-task (Reach vs VR) session pairs with tracked neurons · mouse · n = 18 pairs from 9 mice; 1,521 L5PT and 2,096 GrCs reliable in both tasks
  • Same-task cross-day control session pairs · mouse · n = 9 pairs from 7 mice
  • Novice cross-task session pairs acquired right after pre-training · mouse · n = 9 pairs from 9 mice
  • Optogenetic GrC inhibition during the delay period in Gabra6-Cre×stGtACR1 mice · mouse · n = 4 female mice (4 sessions per task)
  • Simulated cerebellar-like networks (relay, high-rank expansion, low-rank rotation) on alternating two-task manifold prediction · n = 20 random seeds per architecture
Methods & tools
jRGECO1a, GCaMP6f, AAVretro-EF1a-Flpo / AAV1-Ef1a-fDIO-jRGECO1a, stGtACR1 (Gabra6-Cre), custom dual-site two-photon microscope, ScanImage (MBF vDAQ), NoRMCorre, cNMF, ViRMEn, LabVIEW (CompactRIO), MATLAB, scipy.optimize.curve_fit
Reproducibility gaps
Code (Zenodo, DOI 10.5281/zenodo.21461929) and data (Dryad, DOI 10.5061/dryad.9p8cz8x0p) are cited only as DOIs, with no URLs. No software versions, environment files or compute details are stated; analyses used MATLAB and the simulations used Python.
Limitations (6)
  • Where the cross-task transformation arises is unresolved: it may originate in GrCs or be partly inherited from other pre-cerebellar mossy fiber inputs that also remap between contexts. · stated by the authors
  • Matching representational geometry does not imply that L5PT and GrC states follow the same underlying dynamical system. · stated by the authors
  • Smoothness is an interpretation drawn from the computational models, not a quantity measured in the neural data. · stated by the authors
  • Only two contexts were studied, and the out-of-plane elongation effect lost significance when all tracked cells were included regardless of reliability (p=0.4). · stated by the authors
  • In the simulation the Rotation model's task-specific rotation and shear are imposed by hand rather than learned, so the model tests the benefit of reorientation, not how GrCs could produce it. · noted in this summary
  • The cohort is modest (18 cross-task pairs from 9 mice), and the link to learning is correlational. Optogenetics silenced GrCs wholesale, so the trajectory rotation itself was never causally tested. · noted in this summary

Read this if you study cortico-cerebellar computation, neural manifolds or continual learning and want evidence that an expansion layer can separate contexts by reorienting low-rank trajectories instead of expanding them.

Citations
2
FWCI
8.33
Field percentile
top 2%

Abstract

To learn effectively, animals must generalize across yet distinguish between related contexts. Generalization relies on low-dimensional neural manifolds found throughout the neocortex1,2, which accelerate learning by constraining neural activity to task-relevant axes3. Conversely, context separation is attributed to neural expansion layers that can project information into high-dimensional feature spaces4,5, most famously cerebellar granule cells (GrCs)6-8. To investigate the generalization-separation tradeoff, we simultaneously imaged key nodes in the universal cortico-cerebellar pathway9--premotor layer 5 pyramidal tract (L5PT) and GrCs--during parallel learning of two distinct skills with shared temporal structure. Rather than expanding the cortical representations, GrCs retained their low-rank encoding of each task. Across contexts, despite stable cortico-cerebellar coupling, L5PT activity patterns generalized while GrC patterns temporally remapped. But rather than independently scrambling, GrC populations remapped coherently: their low-dimensional trajectories "rotated" apart between tasks, separating the contexts while preserving the cortical geometry of each. Moreover, GrC trajectories diverged most strongly in expert animals. This suggests a fundamental architectural division of labor: the cortex provides invariant dynamic primitives for smooth generalization, while cerebellar activity reconfigures them to drive context-specific output.

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