title: Global scaling down of excitatory postsynaptic responses in cerebellar Purkinje cells impairs developmental synapse elimination.
abstract: Synapse elimination is crucial for precise neural circuit formation during postnatal development. We examined how relative differences in synaptic strengths among competing inputs and/or absolute synaptic strengths contribute to climbing fiber (CF) to Purkinje cell (PC) synapse elimination in the cerebellum. We generated mice with PC-selective deletion of stargazin (TARP γ-2), the major AMPA receptor auxiliary subunit in PCs (γ-2 PC-KO mice). Whereas relative differences between "strong" and "weak" CF-mediated postsynaptic response are preserved, absolute strengths of CF inputs are scaled down globally in PCs of γ-2 PC-KO mice. Although the early phase of CF elimination is normal, dendritic translocation of the strongest CF and the late phase of CF elimination that requires Ca(2+)-dependent activation of Arc/Arg3.1 in PCs are both impaired in γ-2 PC-KO mice. We conclude that, although relative differences in CF synaptic inputs are initially essential, proper synaptic scaling is crucial for accomplishing CF synapse elimination.
authors.affiliation: Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kawata
authors.affiliation: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
authors.forename: Maya
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Takayasu
authors.initials: T
authors.lastname: Mikuni
authors.affiliation: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Yamasaki
authors.affiliation: Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Department of Neurophysiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.affiliation: Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: mkano-tky@m.u-tokyo.ac.jp.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kano
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development; D003598:Cytoskeletal Proteins / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials; D018345:Mice, Knockout; D009415:Nerve Net; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity; D011689:Purkinje Cells / Q000502:physiology*; D018091:Receptors, AMPA / Q000378:metabolism; D013569:Synapses / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C092069:activity regulated cytoskeletal-associated protein