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Territories of heterologous inputs onto Purkinje cell dendrites are segregated by mGluR1-dependent parallel fiber synapse elimination

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Title: Territories of heterologous inputs onto Purkinje cell dendrites are segregated by mGluR1-dependent parallel fiber synapse elimination
Other Titles: mGluR1-mediated parallel fiber synapse elimination
Authors: Ichikawa, Ryoichi Browse this author →KAKEN DB
Hashimoto, Kouichi Browse this author →KAKEN DB
Miyazaki, Taisuke Browse this author →KAKEN DB
Uchigashima, Motokazu Browse this author →KAKEN DB
Yamasaki, Miwako Browse this author →KAKEN DB
Aiba, Atsu Browse this author →KAKEN DB
Kano, Masanobu Browse this author →KAKEN DB
Watanabe, Masahiko Browse this author →KAKEN DB
Keywords: cerebellum
Purkinje cell
dendrite
climbing fiber
parallel fiber
synapse elimination
Issue Date: 23-Feb-2016
Publisher: National Academy of Sciences
Journal Title: Proceedings of the National Academy of Sciences of the United States of America (PNAS)
Volume: 113
Issue: 8
Start Page: 2282
End Page: 2287
Publisher DOI: 10.1073/pnas.1511513113
Abstract: In Purkinje cells (PCs) of the cerebellum, a single "winner" climbing fiber (CF) monopolizes proximal dendrites, whereas hundreds of thousands of parallel fibers (PFs) innervate distal dendrites, and both CF and PF inputs innervate a narrow intermediate domain. It is unclear how this segregated CF and PF innervation is established on PC dendrites. Through reconstruction of dendritic innervation by serial electron microscopy, we show that from postnatal day 9–15 in mice, both CF and PF innervation territories vigorously expand because of an enlargement of the region of overlapping innervation. From postnatal day 15 onwards, segregation of these territories occurs with robust shortening of the overlapping proximal region. Thus, innervation territories by the heterologous inputs are refined during the early postnatal period. Intriguingly, this transition is arrested in mutant mice lacking the type 1 metabotropic glutamate receptor (mGluR1) or protein kinase Cγ (PKCγ), resulting in the persistence of an abnormally expanded overlapping region. This arrested territory refinement is rescued by lentivirus-mediated expression of mGluR1α into mGluR1-deficient PCs. At the proximal dendrite of rescued PCs, PF synapses are eliminated and free spines emerge instead, whereas the number and density of CF synapses are unchanged. Because the mGluR1-PKCγ signaling pathway is also essential for the late-phase of CF synapse elimination, this signaling pathway promotes the two key features of excitatory synaptic wiring in PCs, namely CF monoinnervation by eliminating redundant CF synapses from the soma, and segregated territories of CF and PF innervation by eliminating competing PF synapses from proximal dendrites.
Type: article (author version)
URI: http://hdl.handle.net/2115/62698
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 渡邉 雅彦

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