Magown Philippe, Rafuse Victor F, Brownstone Robert M
Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.
Department of Surgery (Neurosurgery), Dalhousie University, Halifax, Nova Scotia, Canada.
J Neurophysiol. 2017 Apr 1;117(4):1683-1689. doi: 10.1152/jn.00943.2016. Epub 2017 Feb 1.
Motoneurons derived from embryonic stem cells can be transplanted in the tibial nerve, where they extend axons to functionally innervate target muscle. Here, we studied spontaneous muscle contractions in these grafts 3 mo following transplantation. One-half of the transplanted grafts generated rhythmic muscle contractions of variable patterns, either spontaneously or in response to brief electrical stimulation. Activity generated by transplanted embryonic stem cell-derived neurons was driven by glutamate and was modulated by muscarinic and GABAergic/glycinergic transmission. Furthermore, rhythmicity was promoted by the same transmitter combination that evokes rhythmic locomotor activity in spinal cord circuits. These results demonstrate that there is a degree of self-assembly of microcircuits in these peripheral grafts involving embryonic stem cell-derived motoneurons and interneurons. Such spontaneous activity is reminiscent of embryonic circuit development in which spontaneous activity is essential for proper connectivity and function and may be necessary for the grafts to form functional connections with muscle. This manuscript demonstrates that, following peripheral transplantation of neurons derived from embryonic stem cells, the grafts are spontaneously active. The activity is produced and modulated by a number of transmitter systems, indicating that there is a degree of self-assembly of circuits in the grafts.
源自胚胎干细胞的运动神经元可移植到胫神经中，在那里它们延伸轴突以功能性地支配靶肌肉。在此，我们研究了移植后3个月这些移植物中的自发肌肉收缩情况。一半的移植移植物自发地或在短暂电刺激后产生了模式各异的节律性肌肉收缩。移植的胚胎干细胞衍生神经元产生的活动由谷氨酸驱动，并受毒蕈碱和GABA能/甘氨酸能传递的调节。此外，相同的递质组合促进了节律性，该组合在脊髓回路中引发节律性运动活动。这些结果表明，在这些外周移植物中存在一定程度的微电路自组装，涉及胚胎干细胞衍生的运动神经元和中间神经元。这种自发活动让人联想到胚胎回路发育，其中自发活动对于正确的连接和功能至关重要，并且可能是移植物与肌肉形成功能连接所必需的。这篇论文表明，在将源自胚胎干细胞的神经元进行外周移植后，移植物会自发活动。这种活动由多种递质系统产生和调节，表明移植物中存在一定程度的电路自组装。
