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首页> 外文期刊>Neuron >Activity regulates positive and negative neurotrophin-derived signals to determine axon competition.
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Activity regulates positive and negative neurotrophin-derived signals to determine axon competition.

机译：活动调节阳性和阴性的神经营养素衍生信号，以确定轴突竞争。

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Developmental axon competition plays a key role in sculpting neural circuitry. Here, we have asked how activity and neurotrophins could interact to select one axon over another. Using compartmented cultures of sympathetic neurons, we show that, in the presence of NGF, local depolarization confers a competitive growth advantage on the depolarized axon collaterals and at the same time disadvantages the growth of unstimulated axons from the same and competing neurons. Depolarization mediates the competitive advantage by activating a CaMKII-MEK pathway, which converges to enhance local NGF-mediated downstream growth signals. Patterned electrical stimulation also acts via this pathway to enhance NGF-promoted axonal growth. In contrast, the competitive disadvantage is due to BDNF secreted from and acting on the unstimulated, competing axons through p75NTR. Thus, activity regulates both positive and negative neurotrophin-derived signaling cascades to confer a competitive growth advantage on one axon versus another, thereby providing a cellular mechanism for developmental axon selection.
机译：发育性轴突竞争在雕刻神经回路中起关键作用。在这里，我们问活性和神经营养蛋白如何相互作用以选择一个轴突而不是另一个轴突。使用交感神经元的分隔培养，我们显示，在NGF的存在下，局部去极化赋予去极化的轴突侧支竞争性增长优势，同时不利于来自相同和竞争神经元的未刺激轴突的生长。去极化通过激活CaMKII-MEK途径来介导竞争优势，该途径会聚合以增强局部NGF介导的下游生长信号。图案化的电刺激也通过该途径起作用，以增强NGF促进的轴突生长。相比之下，竞争劣势是由于BDNF通过p75NTR从不受刺激的竞争性轴突中分泌并起作用。因此，活性调节正性和负性神经营养蛋白衍生的信号级联，从而赋予一个轴突与另一个轴突竞争性的生长优势，从而为发育性轴突选择提供了细胞机制。

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