Dendrites of cerebellar granule cells correctly recognize their target axons for synaptogenesis in vitro
Dendrites of cerebellar granule cells correctly recognize their target axons for synaptogenesis in vitro
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DOI：
10.1073/pnas.0906653106
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发表时间：
2009-08-04
影响因子：
11.1
通讯作者：
Takeichi, Masatoshi
中科院分区：
文献类型：
--
作者：
Ito, Shoko;Takeichi, Masatoshi
神经回路是由神经元之间精确有序的突触连接生成的，这个过程被认为依赖于神经元识别特定伙伴的能力。然而，众所周知，神经元与非特异性伙伴混杂地形成突触，特别是在体外培养时，引起了关于神经识别机制的争议。在这里，我们重新审视神经元是否能够在体外选择特定的伴侣。在小脑中，颗粒细胞（GC）树突专门与苔藓纤维形成突触连接，但不与攀爬纤维形成突触连接。我们将 GC 神经元与桥脑或下橄榄轴突（分别是苔藓纤维和攀缘纤维的主要来源）以及海马轴突作为对照共培养。 GC神经元与脑桥轴突主要在树突远端形成突触，再现了体内观察到的突触的特征形态，但当与其他轴突结合时，它们却无法做到这一点。在后一种情况下，突触蛋白可以在轴突和树突之间积聚，但这些突触随机分布在整个接触位点，而且它们的突触小泡回收是异常的。这些观察结果表明，即使在体外，GC 树突也可以选择其真正的突触发生伙伴，仅与它们一起形成具有 GC 特异性的突触。
Neural circuits are generated by precisely ordered synaptic connections among neurons, and this process is thought to rely on the ability of neurons to recognize specific partners. However, it is also known that neurons promiscuously form synapses with nonspecific partners, in particular when cultured in vitro, causing controversies about neural recognition mechanisms. Here we reexamined whether neurons can or cannot select particular partners in vitro. In the cerebellum, granule cell ( GC) dendrites form synaptic connections specifically with mossy fibers, but not with climbing fibers. We cocultured GC neurons with pontine or inferior olivary axons, the major sources for mossy and climbing fibers, respectively, as well as with hippocampal axons as a control. The GC neurons formed synapses with pontine axons predominantly at the distal ends of their dendrites, reproducing the characteristic morphology of their synapses observed in vivo, whereas they failed to do so when combined with other axons. In the latter case, synaptic proteins could accumulate between axons and dendrites, but these synapses were randomly distributed throughout the contact sites, and also their synaptic vesicle recycling was anomalous. These observations suggest that GC dendrites can select their authentic partners for synaptogenesis even in vitro, forming the synapses with a GC-specific nature only with them.