title: Territories of heterologous inputs onto Purkinje cell dendrites are segregated by mGluR1-dependent parallel fiber synapse elimination.
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.
authors: Department of Anatomy, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; richi@sapmed.ac.jp watamasa@med.hokudai.ac.jp.
authors: Ryoichi
authors: R
authors: Ichikawa
authors: Department of Neurophysiology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan;
authors: Kouichi
authors: K
authors: Hashimoto
authors: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan;
authors: Taisuke
authors: T
authors: Miyazaki
authors: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan;
authors: Motokazu
authors: M
authors: Uchigashima
authors: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan;
authors: Miwako
authors: M
authors: Yamasaki
authors: Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan;
authors: Atsu
authors: A
authors: Aiba
authors: Department of Neurophysiology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
authors: Masanobu
authors: M
authors: Kano
authors: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan; richi@sapmed.ac.jp watamasa@med.hokudai.ac.jp.
authors: Masahiko
authors: M
authors: Watanabe
mesh_terms: D000818:Animals; D003712:Dendrites / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008959:Models, Neurological; D011493:Protein Kinase C / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D011689:Purkinje Cells / Q000502:physiology* / Q000648:ultrastructure; D018094:Receptors, Metabotropic Glutamate / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology
chemical_list: D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C087857:protein kinase C gamma; D011493:Protein Kinase C
keywords: Purkinje cell; cerebellum; climbing fiber; parallel fiber synapse elimination