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Multiple Phases of Climbing Fiber Synapse Elimination in the Developing Cerebellum

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Abstract

Functional neural circuits in the mature animals are shaped during postnatal development by elimination of unnecessary synapses and strengthening of necessary ones among redundant synaptic connections formed transiently around birth. In the cerebellum of neonatal rodents, excitatory synapses are formed on the somata of Purkinje cells (PCs) by climbing fibers (CFs) that originate from neurons in the contralateral inferior olive. Each PC receives inputs from multiple (~ five) CFs that have about equal synaptic strengths. Subsequently, a single CF selectively becomes stronger relative to the other CFs during the first postnatal week. Then, from around postnatal day 9 (P9), only the strongest CF (“winner” CF) extends its synaptic territory along PC dendrites. In contrast, synapses of the weaker CFs (“loser” CFs) remain on the soma and the most proximal portion of the dendrite together with somatic synapses of the “winner” CF. These perisomatic CF synapses are eliminated progressively during the second and the third postnatal weeks. From P6 to P11, the elimination proceeds independently of the formation of the synapses on PC dendrites by parallel fibers (PFs). From P12 and thereafter, the elimination requires normal PF-PC synapse formation and is presumably dependent on the PF synaptic inputs. Most PCs become mono-innervated by single strong CFs on their dendrites in the third postnatal week. In this review article, we will describe how adult-type CF mono-innervation of PC is established through these multiple phases of postnatal cerebellar development and make an overview of molecular/cellular mechanisms underlying them.

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Funding

This work has been supported in part by Grants-in-Aid for Scientific Research (25000015 to M.K., 24220007 to M.W.) from JSPS, Japan, by Brain/MINDS from AMED, Japan, and by SRPBS from AMED, Japan.

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  1. Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Tokyo, 113-0033, Japan

    Masanobu Kano, Takaki Watanabe & Naofumi Uesaka

  2. International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo Institutes for Advanced Study (UTIAS), The University of Tokyo, Tokyo, 113-0033, Japan

    Masanobu Kano & Takaki Watanabe

  3. Department of Anatomy, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan

    Masahiko Watanabe

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  1. Masanobu Kano
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Kano, M., Watanabe, T., Uesaka, N. et al. Multiple Phases of Climbing Fiber Synapse Elimination in the Developing Cerebellum. Cerebellum 17, 722–734 (2018). https://doi.org/10.1007/s12311-018-0964-z

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