Miyazaki, T Hashimoto, K Shin, HS Kano, M Watanabe, M 2024-01-21T07:34:57Z 2024-01-21T07:34:57Z 2021-09-02 2004-02-18 0270-6474 https://pubs.kist.re.kr/handle/201004/137846 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. English SOC NEUROSCIENCE LONG-TERM DEPRESSION VESICULAR GLUTAMATE TRANSPORTERS CLIMBING FIBER INNERVATION MUTANT MICE MULTIPLE INNERVATION RAT CEREBELLUM MOTOR COORDINATION CALCIUM-CHANNELS P-TYPE OLIVOCEREBELLAR RELATIONSHIPS P/Q-type Ca2+ channel alpha 1A regulates synaptic competition on developing cerebellar Purkinje cells Article 10.1523/JNEUROSCI.4208-03.2004 1 JOURNAL OF NEUROSCIENCE, v.24, no.7, pp.1734 - 1743 JOURNAL OF NEUROSCIENCE 24 7 1734 1743 scie scopus 000189035300025 2-s2.0-1242319242 Neurosciences Neurosciences & Neurology Article 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