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Neural Stem Cell Grafts Form Extensive Synaptic Networks that Integrate with Host Circuits after Spinal Cord Injury.
Cell Stem Cell ( IF 23.9 ) Pub Date : 2020-08-05 , DOI: 10.1016/j.stem.2020.07.007
Steven Ceto 1 , Kohei J Sekiguchi 2 , Yoshio Takashima 3 , Axel Nimmerjahn 2 , Mark H Tuszynski 3
Affiliation  

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.



中文翻译:

神经干细胞移植物形成广泛的突触网络,在脊髓损伤后与宿主电路整合。

神经干/祖细胞 (NSPC) 移植物可以整合到脊髓损伤 (SCI) 的部位,并在可以提供功能益处的病变之间产生神经元中继。为了确定移植物是否以及如何形成突触组织并与宿主系统连接,我们在体内SCI 部位和成人脊髓切片中对 NSPC 移植物进行了钙成像。NSPC 移植物组织成局部和自发活跃的突触网络。光遗传学刺激宿主皮质脊髓束轴突再生成移植物,在整个移植物中引起不同且分离的神经元网络反应。此外,从移植物延伸到去神经支配的脊髓的移植物衍生轴突的光遗传学刺激也引发了局部宿主神经元网络反应。体内成像显示行为刺激同样引起移植物内的局灶性突触反应。因此,神经祖细胞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。

更新日期:2020-09-03
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