Hashimoto, Kouichi Tsujita, Mika Miyazaki, Taisuke Kitamura, Kazuo Yamazaki, Maya Shin, Hee-Sup Watanabe, Masahiko Sakimura, Kenji Kano, Masanobu 2024-01-20T17:00:48Z 2024-01-20T17:00:48Z 2021-09-05 2011-06-14 0027-8424 https://pubs.kist.re.kr/handle/201004/130264 Neural circuits are initially redundant but rearranged through activity-dependent synapse elimination during postnatal development. This process is crucial for shaping mature neural circuits and for proper brain function. At birth, Purkinje cells (PCs) in the cerebellum are innervated by multiple climbing fibers (CFs) with similar synaptic strengths. During postnatal development, a single CF is selectively strengthened in each PC through synaptic competition, the strengthened single CF undergoes translocation to a PC dendrite, and massive elimination of redundant CF synapses follows. To investigate the cellular mechanisms of this activity-dependent synaptic refinement, we generated mice with PC-selective deletion of the Ca(v)2.1 P/Q-type Ca2+ channel, the major voltage-dependent Ca2+ channel in PCs. In the PC-selective Ca(v)2.1 knockout mice, Ca2+ transients induced by spontaneous CF inputs are markedly reduced in PCs in vivo. Not a single but multiple CFs were equally strengthened in each PC from postnatal day 5 (P5) to P8, multiple CFs underwent translocation to PC dendrites, and subsequent synapse elimination until around P12 was severely impaired. Thus, P/Q-type Ca2+ channels in postsynaptic PCs mediate synaptic competition among multiple CFs and trigger synapse elimination in developing cerebellum. English NATL ACAD SCIENCES CLIMBING FIBER INNERVATION GLUTAMATE-RECEPTOR DELTA-2 MICE LACKING POSTNATAL-DEVELOPMENT CALCIUM-CHANNELS CRITICAL PERIOD MUTANT MICE SYNAPSES PARALLEL REGRESSION Postsynaptic P/Q-type Ca2+ channel in Purkinje cell mediates synaptic competition and elimination in developing cerebellum Article 10.1073/pnas.1101488108 1 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.108, no.24, pp.9987 - 9992 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 108 24 9987 9992 scie scopus 000291594000051 2-s2.0-79960004690 Multidisciplinary Sciences Science & Technology - Other Topics Article CLIMBING FIBER INNERVATION GLUTAMATE-RECEPTOR DELTA-2 MICE LACKING POSTNATAL-DEVELOPMENT CALCIUM-CHANNELS CRITICAL PERIOD MUTANT MICE SYNAPSES PARALLEL REGRESSION calcium channel inferior olive vesicular glutamate transporter 2 Cre/loxP system alpha 1A subunit