Synaptic signalling in a network of dopamine neurons: what prevents proper intercellular crosstalk?
Synaptic signalling in a network of dopamine neurons: what prevents proper intercellular crosstalk?
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DOI：
10.1002/1873-3468.13910
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发表时间：
2020-08-30
期刊：
影响因子：
3.5
通讯作者：
Sylantyev，Sergiy
中科院分区：
文献类型：
--
作者：
Chen，Yixi;Kunath，Tilo;Sylantyev，Sergiy
人胚胎干细胞（hESC）来源的中脑多巴胺（DA）神经元因其可持续性和一致性优于以前使用的胎儿组织而成为移植的细胞来源。然而，对培养中的 DA 神经元的多项研究未能记录突触输入时动作电位 (AP) 的产生。为了测试这是否是由于星形胶质细胞释放的 NMDA 受体 (NMDAR) 激动剂缺乏所致，我们研究了 hESC 衍生的 DA 神经元培养物中神经受体的功能特性。我们发现，除了共激动剂数量不足之外，神经元间串扰的缺乏是由于突触 NMDAR 受到突触释放的 DA 的直接抑制而导致其功能减退。这种抑制性音调独立于 DA 受体，并影响 NMDAR 共激动剂结合位点。
Human embryonic stem cell (hESC)‐derived midbrain dopamine (DA) neurons stand out as a cell source for transplantation with their sustainability and consistency superior to the formerly used fetal tissues. However, multiple studies of DA neurons in culture failed to register action potential (AP) generation upon synaptic input. To test whether this is due to deficiency of NMDA receptor (NMDAR) coagonists released from astroglia, we studied the functional properties of neural receptors in hESC‐derived DA neuronal cultures. We find that, apart from an insufficient amount of coagonists, lack of interneuronal crosstalk is caused by hypofunction of synaptic NMDARs due to their direct inhibition by synaptically released DA. This inhibitory tone is independent of DA receptors and affects the NMDAR coagonist binding site.