Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy.
Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy.
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DOI：
10.3389/fcell.2021.720078
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发表时间：
2021
影响因子：
5.5
通讯作者：
Chubykin AA
中科院分区：
文献类型：
--
作者：
Tang Y;Wu Q;Gao M;Ryu E;Pei Z;Kissinger ST;Chen Y;Rao AK;Xiang Z;Wang T;Li W;Chen G;Chubykin AA
脑功能下的神经回路容易受到损伤，包括缺血性损伤，导致神经元丢失和神经胶质瘤。最近的内源性星形胶质细胞直接原位转化为神经元的技术可以同时补充神经元群和逆转胶质瘢痕。然而，这些新重编程的神经元是否能正常发育、融入现有的神经元回路并获得该回路特有的功能特性尚不清楚。我们研究了neurod1介导的体内直接重编程对缺血性损伤小鼠视觉皮质回路整合和功能恢复的影响。在对体内重编程细胞进行细胞外电生理记录和双光子钙成像，并在体外将突触连接映射到这些细胞上后，我们发现NeuroD1重编程神经元被整合到皮层微回路中，并获得直接的视觉反应。此外，在视觉体验之后，重编程神经元表现出取向选择性和功能连接的成熟。我们的研究结果表明，neurod1重编程神经元可以成功地发育并整合到视觉皮层回路中，从而导致缺血性损伤后的视力恢复。
Neural circuits underlying brain functions are vulnerable to damage, including ischemic injury, leading to neuronal loss and gliosis. Recent technology of direct conversion of endogenous astrocytes into neurons in situ can simultaneously replenish the neuronal population and reverse the glial scar. However, whether these newly reprogrammed neurons undergo normal development, integrate into the existing neuronal circuit, and acquire functional properties specific for this circuit is not known. We investigated the effect of NeuroD1-mediated in vivo direct reprogramming on visual cortical circuit integration and functional recovery in a mouse model of ischemic injury. After performing electrophysiological extracellular recordings and two-photon calcium imaging of reprogrammed cells in vivo and mapping the synaptic connections formed onto these cells ex vivo, we discovered that NeuroD1 reprogrammed neurons were integrated into the cortical microcircuit and acquired direct visual responses. Furthermore, following visual experience, the reprogrammed neurons demonstrated maturation of orientation selectivity and functional connectivity. Our results show that NeuroD1-reprogrammed neurons can successfully develop and integrate into the visual cortical circuit leading to vision recovery after ischemic injury.
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影响因子：
64.8
作者：
Li, Ye;Van Hooser, Stephen D.;Mazurek, Mark;White, Leonard E.;Fitzpatrick, David
通讯作者：
Fitzpatrick, David
影响因子：
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