2011.06.06
Postsynaptic P/Q-type Ca2+ channel in Purkinje cell mediates synaptic competition and elimination in developing cerebellum
Hashimoto K a,b,c, Tsujita M d, Miyazaki T e, Kitamura K a,c, Yamazaki M d, Shin HS f, Watanabe M e, Sakimura K d, Kano M a.
aDepartment of Neurophysiology, Graduate School of Medicine, University of Tokyo
bDepartment of Neurophysiology, Graduate School of Biomedical Sciences, Hiroshima University,
cPrecursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama
dDepartment of Cellular Neurobiology, Brain Research Institute, Niigata University
eDepartment of Anatomy, Graduate School of Medicine, Hokkaido University
fCenter for Neural Science, Korea Institute of Science and Technology, Korea
Abstract
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 Ca(2+) channel, the major voltage-dependent Ca(2+) channel in PCs. In the PC-selective Ca(v)2.1 knockout mice, Ca(2+) 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 Ca(2+) channels in postsynaptic PCs mediate synaptic competition among multiple CFs and trigger synapse elimination in developing cerebellum.
*Reprinted with permission from the copyright owner.
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