Neural Stem Cell Grafts Form Extensive Synaptic Networks that Integrate with Host Circuits after Spinal Cord Injury
Neural Stem Cell Grafts Form Extensive Synaptic Networks that Integrate with Host Circuits after Spinal Cord Injury
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DOI：
10.1016/j.stem.2020.07.007
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发表时间：
2020-09-03
期刊：
影响因子：
23.9
通讯作者：
Tuszynski, Mark H.
中科院分区：
文献类型：
--
作者：
Ceto, Steven;Sekiguchi, Kohei J.;Tuszynski, Mark H.
神经干/祖细胞（NSPC）移植物可以整合到脊髓损伤（SCI）的部位，并产生跨病变的神经元中继，可以提供功能益处。为了确定移植物是否以及如何成为突触组织并与宿主系统连接，我们对体内SCI部位和成人脊髓切片中的NSPC移植物进行了钙成像。NSPC移植物组织成局部的和自发活跃的突触网络。光遗传刺激宿主皮质脊髓束轴突再生成移植物引起不同的和隔离的神经元网络的反应，整个移植物。此外，从移植物延伸到失神经脊髓的移植物衍生轴突的光遗传学刺激也触发了局部宿主神经元网络反应。在体内成像显示，行为刺激同样引起局灶性突触反应内移植。因此，神经前体移植物可以形成功能性突触子网络，其活动模式类似于完整的脊髓。
Neural stem/progenitor cell (NSPC) grafts can integrate into sites of spinal cord injury (SCI) and generate neuronal relays across lesions that can provide functional benefit. To determine if and how grafts become synaptically organized and connect with host systems, we performed calcium imaging of NSPC grafts in SCI sites in vivo and in adult spinal cord slices. NSPC grafts organize into localized and spontaneously active synaptic networks. Optogenetic stimulation of host corticospinal tract axons regenerating into grafts elicited distinct and segregated neuronal network responses throughout the graft. Moreover, optogenetic stimulation of graft-derived axons extending from the graft into the denervated spinal cord also triggered local host neuronal network responses. In vivo imaging revealed that behavioral stimulation likewise elicited focal synaptic responses within grafts. Thus neural progenitor grafts can form functional synaptic subnetworks whose activity patterns resemble intact spinal cord.