Calcium Signaling and Cerebellar Synaptic Circuit Development

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Synapse formation depends critically on the competition among inputs of multiple sources to individual neurons. Cerebellar Purkinje cells have highly organized synaptic wiring from two distinct sources of excitatory afferents. Single climbing fibers innervate proximal dendrites of Purkinje cells, whereas numerous parallel fibers converge on their distal dendrites. Here, we demonstrate that the P/Q-type Ca^<2+> channel a1A, a major Ca^<2+> channel subtype in Purkinje cells, is crucial for this organized synapse formation. In the alA knockout mouse, ectopic spine formation was frequently observed in proximal dendrites and somata of Purkinje cells. Innervation territory of parallel fibers was expanded proximally to innervate these ectopic spines, whereas that of climbing fibers was regressed to the basal portion of proximal dendrites and somata. Furthermore, multiple climbing fibers, consisting of a strong climbing fiber and one or a few weaker ones, persisted in the majority of Purkinje cells and were co-wired to the basal somatodendritic domain. The lack of alA, therefore, results in the survival of parallel fibers and surplus climbing fibers, which should normally be expelled from the compartment innervated by the main climbing fiber. We conclude that a P/Q-type Ca^<2+> channel alA fuels both heterosynaptic competition between climbing fibers and parallel fibers and homosynaptic competition among multiple climbing fibers. This molecular function facilitates the distal extension of climbing fiber innervation along Purkinje cell's dendritic tree and also establishes mono climbing fiber innervation of individual Purkinje cells.