P/Q-type Ca2+ channel alpha 1A regulates synaptic competition on developing cerebellar Purkinje cells

Authors
Miyazaki, THashimoto, KShin, HSKano, MWatanabe, M
Issue Date
2004-02-18
Publisher
SOC NEUROSCIENCE
Citation
JOURNAL OF NEUROSCIENCE, v.24, no.7, pp.1734 - 1743
Abstract
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.
Keywords
LONG-TERM DEPRESSION; VESICULAR GLUTAMATE TRANSPORTERS; CLIMBING FIBER INNERVATION; MUTANT MICE; MULTIPLE INNERVATION; RAT CEREBELLUM; MOTOR COORDINATION; CALCIUM-CHANNELS; P-TYPE; OLIVOCEREBELLAR RELATIONSHIPS; LONG-TERM DEPRESSION; VESICULAR GLUTAMATE TRANSPORTERS; CLIMBING FIBER INNERVATION; MUTANT MICE; MULTIPLE INNERVATION; RAT CEREBELLUM; MOTOR COORDINATION; CALCIUM-CHANNELS; P-TYPE; OLIVOCEREBELLAR RELATIONSHIPS; cerebellum; Purkinje cell; climbing fiber; parallel fiber; P/Q-type calcium channel; alpha 1A subunit; development; synapse formation
ISSN
0270-6474
URI
https://pubs.kist.re.kr/handle/201004/137846
DOI
10.1523/JNEUROSCI.4208-03.2004
Appears in Collections:
KIST Article > 2004
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