Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy
Autor: | Samuel T. Kissinger, Abhinav K. Rao, Gong Chen, Qiuyu Wu, Esther Ryu, Mang Gao, Tao Wang, Yuchen Chen, Alexander A. Chubykin, Zifei Pei, Zongqin Xiang, Yu Tang, Wen Li |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
QH301-705.5
two-photon calcium imaging NeuroD1 Biology orientation selectivity Glial scar Cell and Developmental Biology Calcium imaging medicine Biological neural network visual cortex Biology (General) Original Research circuit mapping functional circuit recovery Cell Biology gene therapy Electrophysiology Visual cortex medicine.anatomical_structure Gliosis nervous system NEUROD1 medicine.symptom Neuroscience Reprogramming ischemic injury Developmental Biology |
Zdroj: | Frontiers in Cell and Developmental Biology, Vol 9 (2021) Frontiers in Cell and Developmental Biology |
Popis: | 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. |
Databáze: | OpenAIRE |
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