Purkinje Cell Spatial Correlation Dynamics Are Key to Cerebellar Cortical Contributions to Behavior

浦肯野细胞空间相关动力学是小脑皮层对行为贡献的关键

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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 Ca(2+) imaging of the cerebellar cortex. We performed wide-field cerebellar recordings in mice of both sexes exhibiting sparse expression of the Ca(2+) 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 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.

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