Traveling waves in developing cerebellar cortex mediated by asymmetrical Purkinje cell connectivity

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Abstract
The authors use patch-clamp recordings and two-photon microscopy to characterize monosynaptic connections between Purkinje cells of the juvenile cerebellum. They then construct a network model that generates traveling waves of activity between connected Purkinje cells and validate their model with observations in juvenile cerebellar cortex. Correlated network activity is important in the development of many neural circuits. Purkinje cells are among the first neurons to populate the cerebellar cortex, where they sprout exuberant axon collaterals. We used multiple patch-clamp recordings targeted with two-photon microscopy to characterize monosynaptic connections between the Purkinje cells of juvenile mice. We found that Purkinje cell axon collaterals projected asymmetrically in the sagittal plane, directed away from the lobule apex. On the basis of our anatomical and physiological characterization of this connection, we constructed a network model that robustly generated waves of activity that traveled along chains of connected Purkinje cells. Consistent with the model, we observed traveling waves of activity in Purkinje cells in sagittal slices from young mice that require GABAA receptor–mediated transmission and intact Purkinje cell axon collaterals. These traveling waves are absent in adult mice, suggesting they have a developmental role in wiring the cerebellar cortical microcircuit.