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Retrograde BDNF to TrkB signaling promotes synapse elimination in the developing cerebellum

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  • Myeongjeong Choo

    (The University of Tokyo)

  • Taisuke Miyazaki

    (Hokkaido University Graduate School of Medicine)

  • Maya Yamazaki

    (Brain Research Institute, Niigata University)

  • Meiko Kawamura

    (Brain Research Institute, Niigata University)

  • Takanobu Nakazawa

    (The University of Tokyo)

  • Jianling Zhang

    (The University of Tokyo)

  • Asami Tanimura

    (The University of Tokyo)

  • Naofumi Uesaka

    (The University of Tokyo)

  • Masahiko Watanabe

    (Hokkaido University Graduate School of Medicine)

  • Kenji Sakimura

    (Brain Research Institute, Niigata University)

  • Masanobu Kano

    (The University of Tokyo)

Abstract

Elimination of early-formed redundant synapses during postnatal development is essential for functional neural circuit formation. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs). A single CF is strengthened whereas the other CFs are eliminated in each PC dependent on postsynaptic activity in PC, but the underlying mechanisms are largely unknown. Here, we report that brain-derived neurotrophic factor (BDNF) from PC facilitates CF synapse elimination. By PC-specific deletion of BDNF combined with knockdown of BDNF receptors in CF, we show that BDNF acts retrogradely on TrkB in CFs, and facilitates elimination of CF synapses from PC somata during the third postnatal week. We also show that BDNF shares signaling pathway with metabotropic glutamate receptor 1, a key molecule that triggers a canonical pathway for CF synapse elimination. These results indicate that unlike other synapses, BDNF mediates punishment signal for synapse elimination in the developing cerebellum.

Suggested Citation

  • Myeongjeong Choo & Taisuke Miyazaki & Maya Yamazaki & Meiko Kawamura & Takanobu Nakazawa & Jianling Zhang & Asami Tanimura & Naofumi Uesaka & Masahiko Watanabe & Kenji Sakimura & Masanobu Kano, 2017. "Retrograde BDNF to TrkB signaling promotes synapse elimination in the developing cerebellum," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00260-w
    DOI: 10.1038/s41467-017-00260-w
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