Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy
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....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.720078/full |
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| author | Yu Tang Qiuyu Wu Mang Gao Esther Ryu Zifei Pei Samuel T. Kissinger Yuchen Chen Abhinav K. Rao Zongqin Xiang Tao Wang Wen Li Gong Chen Gong Chen Alexander A. Chubykin |
| author_facet | Yu Tang Qiuyu Wu Mang Gao Esther Ryu Zifei Pei Samuel T. Kissinger Yuchen Chen Abhinav K. Rao Zongqin Xiang Tao Wang Wen Li Gong Chen Gong Chen Alexander A. Chubykin |
| author_sort | Yu Tang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T23:15:42Z |
| format | Article |
| id | doaj.art-ea42dc4bfe47474583ff8f30bda38955 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-21T23:15:42Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-ea42dc4bfe47474583ff8f30bda389552022-12-21T18:46:56ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-08-01910.3389/fcell.2021.720078720078Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene TherapyYu Tang0Qiuyu Wu1Mang Gao2Esther Ryu3Zifei Pei4Samuel T. Kissinger5Yuchen Chen6Abhinav K. Rao7Zongqin Xiang8Tao Wang9Wen Li10Gong Chen11Gong Chen12Alexander A. Chubykin13Department of Biological Sciences, Purdue Institute for Integrative Neuroscience, Purdue Autism Research Center, Purdue University, West Lafayette, IN, United StatesDepartment of Biological Sciences, Purdue Institute for Integrative Neuroscience, Purdue Autism Research Center, Purdue University, West Lafayette, IN, United StatesDepartment of Biological Sciences, Purdue Institute for Integrative Neuroscience, Purdue Autism Research Center, Purdue University, West Lafayette, IN, United StatesDepartment of Biological Sciences, Purdue Institute for Integrative Neuroscience, Purdue Autism Research Center, Purdue University, West Lafayette, IN, United StatesDepartment of Biology, Huck Institutes of Life Sciences, Pennsylvania State University, University Park, PA, United StatesDepartment of Biological Sciences, Purdue Institute for Integrative Neuroscience, Purdue Autism Research Center, Purdue University, West Lafayette, IN, United StatesDepartment of Biology, Huck Institutes of Life Sciences, Pennsylvania State University, University Park, PA, United StatesDepartment of Biology, Huck Institutes of Life Sciences, Pennsylvania State University, University Park, PA, United StatesGuangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, ChinaGuangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, ChinaGuangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, ChinaDepartment of Biology, Huck Institutes of Life Sciences, Pennsylvania State University, University Park, PA, United StatesGuangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, ChinaDepartment of Biological Sciences, Purdue Institute for Integrative Neuroscience, Purdue Autism Research Center, Purdue University, West Lafayette, IN, United StatesNeural 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.720078/fullNeuroD1gene therapyfunctional circuit recoveryischemic injuryvisual cortexcircuit mapping |
| spellingShingle | Yu Tang Qiuyu Wu Mang Gao Esther Ryu Zifei Pei Samuel T. Kissinger Yuchen Chen Abhinav K. Rao Zongqin Xiang Tao Wang Wen Li Gong Chen Gong Chen Alexander A. Chubykin Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy Frontiers in Cell and Developmental Biology NeuroD1 gene therapy functional circuit recovery ischemic injury visual cortex circuit mapping |
| title | Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy |
| title_full | Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy |
| title_fullStr | Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy |
| title_full_unstemmed | Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy |
| title_short | Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy |
| title_sort | restoration of visual function and cortical connectivity after ischemic injury through neurod1 mediated gene therapy |
| topic | NeuroD1 gene therapy functional circuit recovery ischemic injury visual cortex circuit mapping |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.720078/full |
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