Purkinje cell spatial correlation dynamics are key to cerebellar cortical contributions to behavior.

Abstract

A major challenge in cerebellar physiology is determining how the stereotypic, conserved circuitry of the cerebellar cortex, with its dominant parasagittal and transverse architectures, underlies its fundamental computations and contributions to behavior. Recent advances have allowed for the resolution of Purkinje cell dendritic activity at large scales, but the full roles of these Purkinje cell dynamics during behavior remain undetermined. To interrogate Purkinje cell dynamics at the population level during behavior, we implemented a novel approach for awake, chronic, wide-field Ca2+ imaging of the cerebellar cortex. We performed wide-field cerebellar recordings in mice of both sexes exhibiting sparse expression of the Ca2+ indicator GCaMP6s, which importantly allowed for the resolution of both dendritic and somatic Purkinje cell activity. Blind source separation of wide-field dynamics using spatial independent component analysis (sICA) extracts components consisting of either Purkinje cell dendrites or somata, with distinct activity and spatial properties. These independent components (ICs) tend to be either parasagittally organized and likely reflective of dendritic activity, or more spatially distributed populations of Purkinje cell somata. We observe broad, bilateral activation of both these dendritic and somatic ICs during behavior, but they exhibit distinct and divergent patterns of spatial correlations occurring primarily along the parasagittal and transverse directions, consistent with the main geometry of the cerebellar cortex. Somatic correlation dynamics are robustly modulated by prediction errors and reflect ultimate behavioral outcomes. These results provide a novel link between cerebellar structure and function, with the correlation dynamics of Purkinje cell activity a key feature during behavior.Significance statement The cerebellar cortex exhibits highly conserved, elegant cytoarchitecture, but a full understanding of how this organization contributes to cerebellar processing is limited. We performed wide-field Ca2+ recordings of the primary output neurons of the cerebellar cortex, Purkinje cells, and find that they are organized into distinct networks, which are either parasagittally organized or distributed populations of somatic activity. While both networks are highly engaged during behavior, they exhibit distinct spatial correlation dynamics consistent with the main geometry of the cerebellar cortex, with somatic correlation dynamics conveying information about prediction error and behavioral outcomes. Together, these results provide new insights into the functional organization of Purkinje cells and implicate somatic network correlation dynamics as a key feature of cerebellar processing.