MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, University of Edinburgh, Edinburgh, UK.
UK Centre for Mammalian Synthetic Biology, University of Edinburgh, Edinburgh, UK.
FEBS Lett. 2020 Oct;594(20):3272-3292. doi: 10.1002/1873-3468.13910. Epub 2020 Aug 30.
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.
人胚胎干细胞（hESC）衍生的中脑多巴胺（DA）神经元作为移植的细胞来源引人注目，其可持续性和一致性优于以前使用的胎儿组织。然而，在培养中的 DA 神经元的多项研究未能在突触输入时记录动作电位（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）共激动剂缺乏，我们研究了 hESC 衍生的 DA 神经元培养物中的神经受体的功能特性。我们发现，除了共激动剂的数量不足外，由于突触释放的 DA 直接抑制突触 NMDA 受体，神经元之间的串扰缺乏是由于突触 NMDA 受体的功能障碍引起的。这种抑制性音调与 DA 受体无关，并且影响 NMDAR 共激动剂结合位点。
