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Publication : P/Q-type Ca2+ channel alpha1A regulates synaptic competition on developing cerebellar Purkinje cells.

First Author  Miyazaki T Year  2004
Journal  J Neurosci Volume  24
Issue  7 Pages  1734-43
PubMed ID  14973254 Mgi Jnum  J:90116
Mgi Id  MGI:3042538 Doi  10.1523/JNEUROSCI.4208-03.2004
Citation  Miyazaki T, et al. (2004) P/Q-type Ca2+ channel alpha1A regulates synaptic competition on developing cerebellar Purkinje cells. J Neurosci 24(7):1734-43
abstractText  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 Ca2+ channel alpha1A, a major Ca2+ channel subtype in Purkinje cells, is crucial for this organized synapse formation. In the alpha1A knock-out 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 climbing fibers, persisted in the majority of Purkinje cells and were cowired to the same somata, proximal dendrites, or both. Therefore, the lack of alpha1A 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 Ca2+ 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 the dendritic tree of the Purkinje cell and also establishes climbing fiber monoinnervation of individual Purkinje cells.
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