TrkB (tropomyosin-related kinase B) controls the assembly and maintenance of GABAergic synapses in the cerebellar cortex.
TrkB (tropomyosin-related kinase B) controls the assembly and maintenance of GABAergic synapses in the cerebellar cortex.
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DOI：
10.1523/jneurosci.4991-10.2011
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发表时间：
2011-02-23
期刊：
影响因子：
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通讯作者：
Reichardt LF
中科院分区：
文献类型：
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作者：
Chen AI;Nguyen CN;Copenhagen DR;Badurek S;Minichiello L;Ranscht B;Reichardt LF
抑制性中间神经元在协调神经回路的活动中起着关键作用。为了探索抑制回路组织的机制，我们分析了TrkB参与小鼠小脑皮质高尔基体和颗粒细胞之间GABA能抑制性突触的组装和维持。我们发现TrkB直接作用于每种细胞类型，以调节突触分化。TrkB不仅是组装所必需的，而且主要通过调节突触成分的定位来维持这些突触和行为。在突触后，TrkB控制支架蛋白（gephyrin）的定位，但作用于细胞粘附分子（Neuroligin-2）定位之后的步骤。重要的是，在高尔基体和颗粒细胞中定位免疫球蛋白超家族细胞粘附分子Contactin-1需要TrkB，并且Contactin-1的缺乏也导致抑制性突触发育的缺陷。因此，我们的研究结果表明，TrkB控制GABA能突触的组装和维持，并表明TrkB的功能，部分是通过促进突触粘附。
Inhibitory interneurons play a critical role in coordinating the activity of neural circuits. To explore the mechanisms that direct the organization of inhibitory circuits, we analyzed the involvement of TrkB in the assembly and maintenance of GABAergic inhibitory synapses between Golgi and granule cells in the mouse cerebellar cortex. We show that TrkB acts directly within each cell-type to regulate synaptic differentiation. TrkB is required not only for assembly, but also maintenance of these synapses and acts, primarily, by regulating the localization of synaptic constituents. Postsynaptically, TrkB controls the localization of a scaffolding protein, gephyrin, but acts at a step subsequent to the localization of a cell adhesion molecule, Neuroligin-2. Importantly, TrkB is required for the localization of an immunoglobulin superfamily cell adhesion molecule, Contactin-1, in Golgi and granule cells and the absence of Contactin-1 also results in deficits in inhibitory synaptic development. Thus, our findings demonstrate that TrkB controls the assembly and maintenance of GABAergic synapses and suggest that TrkB functions, in part, through promoting synaptic adhesion.