Abstract
NMDA receptors mediate activity-dependent, competitive synaptic refinement in the visual and somatosensory cortices. In cerebellar Purkinje cells, climbing fibers and parallel fibers are competitive to structure territorized dendritic innervation, but Purkinje cells lack functional NMDA receptors. Here, we demonstrate that the P/Q-type Ca channel alpha1A, a major Ca channel subtype in Purkinje cells, is crucial for the competitive synapse formation. In the alpha1A knockout mouse, many ectopic spines were protruded from proximal dendrites and somata of Purkinje cells. Innervation territory of parallel fibers was expanded proximally to innervate the 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 same somata, proximal dendrites, or both. The lack of _lpha1A, therefore, results in the persistence of parallel fibers and surplus climbing fibers, which should normally be expelled from the compartment innervated by the main climbing fiber. These results suggest that a P/Q-type Ca channel alpha1A fuels heterosynaptic competition between climbing fibers and parallel fibers, and also fuels 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 climbing fiber mono-innervation of individual Purkinje cells. [Jpn J Physiol 54 Suppl:S29 (2004)]
