Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.
Neuron. 2011 Jul 28;71(2):235-42. doi: 10.1016/j.neuron.2011.05.045.
A hallmark of mammalian neural circuit development is the refinement of initially imprecise connections by competitive activity-dependent processes. In the developing visual system retinal ganglion cell (RGC) axons from the two eyes undergo activity-dependent competition for territory in the dorsal lateral geniculate nucleus (dLGN). The direct contributions of synaptic transmission to this process, however, remain unclear. We used a genetic approach to reduce glutamate release selectively from ipsilateral-projecting RGCs and found that their release-deficient axons failed to exclude competing axons from the ipsilateral eye territory in the dLGN. Nevertheless, the release-deficient axons consolidated and maintained their normal amount of dLGN territory, even in the face of fully active competing axons. These results show that during visual circuit refinement glutamatergic transmission plays a direct role in excluding competing axons from inappropriate target regions, but they argue that consolidation and maintenance of axonal territory are largely insensitive to alterations in synaptic activity levels.
哺乳动物神经回路发育的一个标志是通过竞争活动依赖性过程来精细调整最初不精确的连接。在发育中的视觉系统中,来自两个眼睛的视网膜神经节细胞(RGC)轴突经历了活动依赖性竞争,以争夺背外侧膝状核(dLGN)中的区域。然而,突触传递对此过程的直接贡献仍不清楚。我们使用一种遗传方法选择性地减少从同侧投射的 RGC 中谷氨酸的释放,发现它们的释放缺陷轴突未能将来自同侧眼的竞争轴突从 dLGN 中的同侧眼区域中排除。尽管如此,释放缺陷的轴突仍然巩固并保持其正常的 dLGN 区域,即使面对完全活跃的竞争轴突也是如此。这些结果表明,在视觉回路细化过程中,谷氨酸能传递在将竞争轴突排除在不合适的靶区中起着直接作用,但它们也表明,轴突区域的巩固和维持在很大程度上不受突触活动水平变化的影响。