Cerebellar climbing fibers convey diverse signals, but how they are organized in the compartmental structure of the cerebellar cortex during learning remains largely unclear. We analyzed a large amount of coordinate-localized two-photon imaging data from cerebellar Crus II in mice undergoing 'Go/No-go' reinforcement learning. Tensor component analysis revealed that a majority of climbing fiber inputs to Purkinje cells were reduced to only four functional components, corresponding to accurate timing control of motor initiation related to a Go cue, cognitive error-based learning, reward processing, and inhibition of erroneous behaviors after a No-go cue. Changes in neural activities during learning of the first two components were correlated with corresponding changes in timing control and error learning across animals, indirectly suggesting causal relationships. Spatial distribution of these components coincided well with boundaries of Aldolase-C/zebrin II expression in Purkinje cells, whereas several components are mixed in single neurons. Synchronization within individual components was bidirectionally regulated according to specific task contexts and learning stages. These findings suggest that, in close collaborations with other brain regions including the inferior olive nucleus, the cerebellum, based on anatomical compartments, reduces dimensions of the learning space by dynamically organizing multiple functional components, a feature that may inspire new-generation AI designs.

Tissue fibrosis affects multiple organs and involves a master-regulatory role of macrophages which respond to an initial inflammatory insult common in all forms of fibrosis. The recently unravelled multi-organ heterogeneity of macrophages in healthy and fibrotic human disease suggests that macrophages expressing osteopontin (SPP1), associate with lung and liver fibrosis. However, the conservation of this SPP1⁺ macrophage population across different tissues, and its specificity to fibrotic diseases with different etiologies remain unclear. Integrating 15 single cell RNA-sequencing datasets to profile 235,930 tissue macrophages from healthy and fibrotic heart, lung, liver, kidney, skin and endometrium, we extended the association of SPP1⁺ macrophages with fibrosis to all these tissues. We also identified a subpopulation expressing matrisome-associated genes (e.g., matrix metalloproteinases and their tissue inhibitors), functionally enriched for ECM remodelling and cell metabolism, representative of a matrisome-associated macrophage (MAM) polarization state within SPP1⁺ macrophages. Importantly, the MAM polarization state follows a differentiation trajectory from SPP1⁺ macrophages and is associated with a core set of regulon activity. SPP1⁺ macrophages without the MAM polarization state (SPP1⁺MAM^-) show a positive association with ageing lung in mice and humans. These results suggest an advanced and conserved polarization state of SPP1⁺ macrophages in fibrotic tissues resulting from prolonged inflammatory cues within each tissue microenvironment.