2024-03-28T17:24:31Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/503762022-11-17T02:08:08Zhdl_2115_20040hdl_2115_121Climbing fiber synapse elimination in cerebellar Purkinje cellsWatanabe, MasahikoKano, Masanobucerebellumclimbing fiberdevelopmentparallel fiberPurkinje cellsynapse elimination491Innervation of Purkinje cells (PCs) by multiple climbing fibers (CFs) is refined into mono-innervation during the first three postnatal weeks of rodents' life. In this review article, we will integrate the current knowledge on developmental process and mechanisms of CF synapse elimination. In the "creeper" stage of CF innervation (postnatal day 0 (P0)∼), CFs creep among PC somata to form transient synapses on immature dendrites. In the "pericellular nest" stage (P5∼), CFs densely surround and innervate PC somata. Then, CF innervation is displaced to the apical portion of PC somata in the "capuchon" stage (P9∼), and translocate to dendrites in the "dendritic" (P12∼) stage. Along with the developmental changes of CF wiring, functional and morphological distinctions become larger among CF inputs. PCs are initially innervated by >5 CFs with similar strengths (∼P3). Only a single CF is selectively strengthened during P3-P7 (functional differentiation), and undergoes dendritic translocation from P9 on (dendritic translocation). Following the functional differentiation, perisomatic CF synapses are eliminated non-selectively, which proceeds in two distinct phases. The early phase (P7-P11) is conducted independently of parallel fiber (PF)-PC synapse formation, while the late phase (P12-P17) critically depends on it. The P/Q-type voltage-dependent Ca2+ channel in PCs triggers selective strengthening of single CF inputs, promotes dendritic translocation of the strengthened CFs, and drives the early phase of CF synapse elimination. On the other hand, the late phase is mediated by mGluR1-Gαq-PLCβ4-PKCγ signaling cascade in PCs driven at PF-PC synapses, whose structural connectivity is stabilized and maintained by the GluRδ2-Cbln1-neurexin system.Wiley-BlackwellJournal Articleapplication/pdfhttp://hdl.handle.net/2115/50376https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/50376/1/EJN34-10_1697-1710.pdf0953-816XEuropean Journal of Neuroscience3410169717102011-11enginfo:pmid/22103426info:doi/10.1111/j.1460-9568.2011.07894.xThe definitive version is available at wileyonlinelibrary.comauthor