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

Myeongjeong Choo, Taisuke Miyazaki, Maya Yamazaki, Meiko Kawamura, Takanobu Nakazawa, Jianling Zhang, Asami Tanimura, Naofumi Uesaka, Masahiko Watanabe, Kenji Sakimura and Masanobu Kano ()
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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

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00260-w

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