Retrograde BDNF to TrkB signaling promotes synapse elimination in the developing cerebellum.
Retrograde BDNF to TrkB signaling promotes synapse elimination in the developing cerebellum.
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DOI：
10.1038/s41467-017-00260-w
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发表时间：
2017-08-04
影响因子：
16.6
通讯作者：
Kano M
中科院分区：
文献类型：
--
作者：
Choo M;Miyazaki T;Yamazaki M;Kawamura M;Nakazawa T;Zhang J;Tanimura A;Uesaka N;Watanabe M;Sakimura K;Kano M
在出生后发育过程中消除早期形成的冗余突触是形成功能神经回路的关键。新生儿小脑中的浦肯野细胞(PC)由多个爬行纤维(CFs)支配。依赖于PC的突触后活动，单个的CF被强化，而其他的CF在每个PC中被消除，但其潜在的机制在很大程度上是未知的。在这里，我们报告了来自PC的脑源性神经营养因子(BDNF)促进了CF突触的消除。通过PC特异性的BDNF缺失和Cf中BDNF受体的敲除，我们发现BDNF在CFS中以逆行的方式作用于TrkB，并有助于在出生后第三周消除PC胞体中的Cf突触。我们还表明，BDNF与代谢性谷氨酸受体1共享信号通路，后者是触发CF突触消除的典型途径的关键分子。这些结果表明，与其他突触不同的是，BDNF在发育中的小脑中介导了突触消除的惩罚信号。在发育过程中，突触通过依赖活动的竞争选择性地加强或消除。在这里，作者表明，BDNF-TrkB逆行信号是一种“惩罚”信号，导致在发育中的小脑中消除攀升的纤维到浦肯野细胞的突触。
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.
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DOI：
10.1073/pnas.092129699
发表时间：
2002-04-30
影响因子：
11.1
作者：
Gärtner, AG;Staiger, V
通讯作者：
Staiger, V
影响因子：
15.9
作者：
Ibáñez, CF
通讯作者：
Ibáñez, CF
影响因子：
64.8
作者：
Finch, EA;Augustine, GJ
通讯作者：
Augustine, GJ
影响因子：
3.3
作者：
BATCHELOR, AM;MADGE, DJ;GARTHWAITE, J
通讯作者：
GARTHWAITE, J
影响因子：
5.3
作者：
Carter, AR;Chen, CF;Segal, RA
通讯作者：
Segal, RA