N-cadherin transsynaptically regulates short-term plasticity at glutamatergic synapses in embryonic stem cell-derived neurons
N-cadherin transsynaptically regulates short-term plasticity at glutamatergic synapses in embryonic stem cell-derived neurons
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DOI：
10.1523/jneurosci.1013-06.2006
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发表时间：
2006-06-28
影响因子：
5.3
通讯作者：
Gottmann, Kurt
中科院分区：
文献类型：
--
作者：
Juengling, Kay;Eulenburg, Volker;Gottmann, Kurt
细胞粘附分子N-钙粘蛋白被认为调节哺乳动物中枢神经元突触的形成。这是基于其突触定位，通过粘附机制实现突触前和突触后特化的对齐。然而，N-钙粘蛋白在调节突触传递中的潜在作用仍然难以捉摸。在本文中，N-钙粘蛋白敲除突触的功能分析，使在体外神经元分化的小鼠胚胎干细胞规避早期胚胎致死的小鼠遗传无效的N-钙粘蛋白。在我们的体外系统中，初始突触的形成没有改变的情况下，N-钙粘蛋白，这可能是由于代偿机制。在这里，我们表明，N-钙粘蛋白是调节突触前神经元突触功能所必需的。在高活动期间，胞吐作用的囊泡可用性受损变得明显。短期的可塑性强烈改变与突触抑制增强N-钙粘蛋白的情况下。最有趣的是，在特定的刺激条件下，易化会转化为抑郁。这表明一个重要的作用，N-钙粘蛋白在控制短期plasticity.To分析，是否N-钙粘蛋白调节突触前功能的跨突触机制，我们研究了嵌合文化组成的野生型新皮层神经元和ES细胞衍生的神经元。与N-钙粘蛋白缺席，只有突触后，我们观察到了类似的增加，在短期突触抑制中发现其完全缺席。这表明N-钙粘蛋白对短期可塑性的逆行控制。总之，我们的研究结果揭示了一个意想不到的参与突触粘附分子在调节短期可塑性在mammatergic突触。
The cell adhesion molecule N-cadherin has been proposed to regulate synapse formation in mammalian central neurons. This is based on its synaptic localization enabling alignment of presynaptic and postsynaptic specializations by an adhesion mechanism. However, a potential role of N-cadherin in regulating synaptic transmission has remained elusive. In this paper, a functional analysis of N-cadherin knock-out synapses was enabled by in vitro neuronal differentiation of mouse embryonic stem cells circumventing the early embryonic lethality of mice genetically null for N-cadherin. In our in vitro system, initial synapse formation was not altered in the absence of N-cadherin, which might be attributable to compensatory mechanisms. Here, we demonstrate that N-cadherin is required for regulating presynaptic function at glutamatergic synapses. An impairment in the availability of vesicles for exocytosis became apparent selectively during high activity. Short-term plasticity was strongly altered with synaptic depression enhanced in the absence of N-cadherin. Most intriguingly, facilitation was converted to depression under specific stimulation conditions. This indicates an important role of N-cadherin in the control of short-term plasticity.To analyze, whether N-cadherin regulates presynaptic function by a transsynaptic mechanism, we studied chimeric cultures consisting of wild-type neocortical neurons and ES cell-derived neurons. With N-cadherin absent only postsynaptically, we observed a similar increase in short-term synaptic depression as found in its complete absence. This indicates a retrograde control of short-term plasticity by N-cadherin. In summary, our results revealed an unexpected involvement of a synaptic adhesion molecule in the regulation of short-term plasticity at glutamatergic synapses.