PMID- 28775326 OWN - NLM STAT- MEDLINE DCOM- 20171212 LR - 20181113 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 8 IP - 1 DP - 2017 Aug 4 TI - Retrograde BDNF to TrkB signaling promotes synapse elimination in the developing cerebellum. PG - 195 LID - 10.1038/s41467-017-00260-w [doi] LID - 195 AB - 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.During development, synapses are selectively strengthened or eliminated by activity-dependent competition. Here, the authors show that BDNF-TrkB retrograde signaling is a "punishment" signal that leads to elimination of climbing fiber-onto-Purkinje cell synapses in the developing cerebellum. FAU - Choo, Myeongjeong AU - Choo M AD - Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan. FAU - Miyazaki, Taisuke AU - Miyazaki T AD - Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan. FAU - Yamazaki, Maya AU - Yamazaki M AD - Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, 951-8585, Japan. FAU - Kawamura, Meiko AU - Kawamura M AD - Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, 951-8585, Japan. FAU - Nakazawa, Takanobu AU - Nakazawa T AD - Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan. FAU - Zhang, Jianling AU - Zhang J AD - Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan. FAU - Tanimura, Asami AU - Tanimura A AD - Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan. FAU - Uesaka, Naofumi AU - Uesaka N AD - Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan. FAU - Watanabe, Masahiko AU - Watanabe M AD - Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan. FAU - Sakimura, Kenji AU - Sakimura K AD - Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, 951-8585, Japan. FAU - Kano, Masanobu AU - Kano M AD - Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan. mkano-tky@m.u-tokyo.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170804 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Brain-Derived Neurotrophic Factor) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Animals, Newborn MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Cerebellum/*growth & development/metabolism MH - Mice MH - Mice, Knockout MH - Purkinje Cells/metabolism MH - Receptor, trkB/genetics/*metabolism MH - Signal Transduction MH - Synapses/genetics/*metabolism PMC - PMC5543168 COIS- The authors declare no competing financial interests. EDAT- 2017/08/05 06:00 MHDA- 2017/12/13 06:00 PMCR- 2017/08/04 CRDT- 2017/08/05 06:00 PHST- 2016/10/23 00:00 [received] PHST- 2017/06/14 00:00 [accepted] PHST- 2017/08/05 06:00 [entrez] PHST- 2017/08/05 06:00 [pubmed] PHST- 2017/12/13 06:00 [medline] PHST- 2017/08/04 00:00 [pmc-release] AID - 10.1038/s41467-017-00260-w [pii] AID - 260 [pii] AID - 10.1038/s41467-017-00260-w [doi] PST - epublish SO - Nat Commun. 2017 Aug 4;8(1):195. doi: 10.1038/s41467-017-00260-w.