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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Differential outgrowth of axons and their branches is regulated by localized calcium transients.
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Differential outgrowth of axons and their branches is regulated by localized calcium transients.

机译：轴突及其分支的差异性生长受局部钙瞬变的调节。

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During development axon outgrowth and branching are independently regulated such that axons can stall or retract while their interstitial branches extend toward targets. Previous studies have shown that guidance cues and intracellular signaling components can promote branching of cortical axons without affecting axon outgrowth. However, the mechanisms that regulate differential outgrowth of axons and their branches are not well understood. Based on our previous work showing the importance of localized repetitive calcium transients in netrin-1-induced cortical axon branching, we sought to investigate the role of calcium signaling in regulating differential outgrowth of axons and their branches. Using fluorescence calcium imaging of dissociated developing cortical neurons, we show that localized spontaneous calcium transients of different frequencies occur in restricted regions of axons and their branches. Higher frequencies occur in more rapidly extending processes whereas lower frequencies occur in processes that stall or retract. Direct induction of localized calcium transients with photolysis of caged calcium induced rapid outgrowth of axonal processes. Surprisingly outgrowth of one axonal process was almost invariably accompanied by simultaneous retraction of another process belonging to the same axon, suggesting a competitive mechanism for differential process outgrowth. Conversely, reducing frequencies of calcium transients with nifedipine and TTX reduced the incidence of differential process outgrowth. Together these results suggest a novel activity-dependent mechanism whereby intrinsic localized calcium transients regulate the competitive growth of axons and their branches. These mechanisms may also be important for the development of cortical connectivity in vivo.
机译：在发育过程中，轴突的生长和分支受到独立调节，以使轴突在其间质分支朝目标延伸时可以停滞或缩回。先前的研究表明，指导信号和细胞内信号传导成分可以促进皮质轴突的分支，而不会影响轴突的生长。但是，调节轴突及其分支的差异性生长的机制尚不十分清楚。基于我们以前的工作表明在netrin-1诱导的皮质轴突分支中局部重复钙瞬变的重要性，我们寻求研究钙信号在调节轴突及其分支的差异性生长中的作用。使用解离的发展皮质神经元的荧光钙成像，我们表明轴突及其分支的受限区域中发生不同频率的局部自发钙瞬变。较高的频率出现在扩展较快的过程中，而较低的频率出现在停滞或缩回的过程中。笼养钙的光解直接诱导局部钙瞬变，引起轴突突迅速生长。令人惊讶地，一个轴突过程的生长几乎总是伴随着同时撤回属于相同轴突的另一个过程，这提示了差异性过程生长的竞争机制。相反，用硝苯地平和TTX降低钙瞬变的频率可减少差异性过程生长的发生。这些结果共同表明了一种新的依赖于活性的机制，由此固有的局部钙瞬变调节了轴突及其分支的竞争性生长。这些机制对于体内皮质连接性的发展也可能很重要。

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