Spontaneous activity promotes synapse formation in a cell-type-dependent manner in the developing retina.
Spontaneous activity promotes synapse formation in a cell-type-dependent manner in the developing retina.
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DOI：
10.1523/jneurosci.0194-12.2012
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发表时间：
2012-04-18
期刊：
影响因子：
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通讯作者：
Kerschensteiner D
中科院分区：
文献类型：
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作者：
Soto F;Ma X;Cecil JL;Vo BQ;Culican SM;Kerschensteiner D
自发活动被认为调节发育中的神经系统的许多部分中的突触发生。然而，这种调节的体内证据很少，几乎完全来自正常活动减少或完全阻断的实验。因此，自发活动本身是否促进突触发生或发挥纯粹的许可作用，仍然不确定。此外，活动如何影响突触动力学以塑造连接性，以及它在神经元之间的影响是均匀的还是依赖于细胞类型的尚不清楚。在缺乏视锥-视杆同源盒基因（Crx）的小鼠中，光感受器（PR）无法与双极细胞（BC）建立正常连接。在这里，我们发现Crx−/−小鼠的视网膜神经节细胞（RGC）在睁开眼睛的时候变得有节奏地过度活跃;这是由于BCs自发释放的谷氨酸增加。这种升高的神经传递增强了BCs和RGC之间的突触发生，而不改变整体电路结构。使用实时成像，我们发现自发活动选择性地调节突触形成的速度，而不是消除，在这个回路中。重建的连接模式的三个BC类型的共享RGC目标进一步揭示，神经传递具体促进形成多突触并置从一个BC类型，而不影响其他两个连接的维护或消除。虽然Crx−/−小鼠的过度活跃仍然存在，但突触数量在4周龄后不会增加，这表明内层视网膜突触细化的关键时期已经关闭。有趣的是，尽管他们的过度活跃，RGC轴突保持正常的眼睛特定的领土和细胞类型特定层的背外侧膝状体核（dLGN）。
Spontaneous activity is thought to regulate synaptogenesis in many parts of the developing nervous system. In vivo evidence for this regulation, however, is scarce and comes almost exclusively from experiments in which normal activity was reduced or blocked completely. Thus, whether spontaneous activity itself promotes synaptogenesis or plays a purely permissive role, remains uncertain. In addition, how activity influences synapse dynamics to shape connectivity and whether its effects among neurons are uniform or cell type-dependent is unclear. In mice lacking the cone-rod homeobox gene (Crx), photoreceptors (PRs) fail to establish normal connections with bipolar cells (BCs). Here, we find that retinal ganglion cells (RGCs) in Crx−/− mice become rhythmically hyperactive around the time of eye-opening; as a result of increased spontaneous glutamate release from BCs. This elevated neurotransmission enhances synaptogenesis between BCs and RGCs, without altering the overall circuit architecture. Using live imaging, we discover that spontaneous activity selectively regulates the rate of synapse formation, not elimination, in this circuit. Reconstructions of the connectivity patterns of three BC types with a shared RGC target further revealed that neurotransmission specifically promotes the formation of multisynaptic appositions from one BC type without affecting the maintenance or elimination of connections from the other two. While hyperactivity in Crx−/− mice persists, synapse numbers do not increase beyond four weeks of age, suggesting closure of a critical period for synaptic refinement in the inner retina. Interestingly, despite their hyperactivity, RGC axons maintain normal eye-specific territories and cell type-specific layers in the dorsolateral geniculate nucleus (dLGN).