Glutamatergic axon-derived BDNF controls GABAergic synaptic differentiation in the cerebellum.
Glutamatergic axon-derived BDNF controls GABAergic synaptic differentiation in the cerebellum.
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DOI：
10.1038/srep20201
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发表时间：
2016-02-01
影响因子：
4.6
通讯作者：
Reichardt LF
中科院分区：
文献类型：
--
作者：
Chen AI;Zang K;Masliah E;Reichardt LF
为了研究抑制性回路构建的调控机制，我们研究了脑源性神经营养因子（BDNF）在小鼠小脑皮质GABA能抑制性突触组装中的作用。我们发现，在小脑，BDNF表达细胞仅限于内部颗粒层（IGL），但BDNF蛋白存在于苔藓纤维，起源于位于小脑外的细胞。与TrkB（BDNF的同源受体）的缺失相反，单独从小脑细胞体中缺失BDNF并不干扰由IGL内颗粒细胞树突上的高尔基体细胞轴突形成的GABA能突触的突触前或突触后成分的定位。相反，我们发现，BDNF来自兴奋性苔藓纤维末梢控制他们的分化。因此，我们的研究结果表明，小脑BDNF主要来源于兴奋性神经元-小脑前核/脊髓神经元，产生苔藓纤维-并促进GABA能突触的形成作为从轴突释放的结果。因此，在小脑内，BDNF优先定位于轴突增强了BDNF促进GABA能突触分化的特异性。
To study mechanisms that regulate the construction of inhibitory circuits, we examined the role of brain-derived neurotrophic factor (BDNF) in the assembly of GABAergic inhibitory synapses in the mouse cerebellar cortex. We show that within the cerebellum, BDNF-expressing cells are restricted to the internal granular layer (IGL), but that the BDNF protein is present within mossy fibers which originate from cells located outside of the cerebellum. In contrast to deletion of TrkB, the cognate receptor for BDNF, deletion of Bdnf from cerebellar cell bodies alone did not perturb the localization of pre- or postsynaptic constituents at the GABAergic synapses formed by Golgi cell axons on granule cell dendrites within the IGL. Instead, we found that BDNF derived from excitatory mossy fiber endings controls their differentiation. Our findings thus indicate that cerebellar BDNF is derived primarily from excitatory neurons—precerebellar nuclei/spinal cord neurons that give rise to mossy fibers—and promotes GABAergic synapse formation as a result of release from axons. Thus, within the cerebellum the preferential localization of BDNF to axons enhances the specificity through which BDNF promotes GABAergic synaptic differentiation.