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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....
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416524/ https://www.ncbi.nlm.nih.gov/pubmed/34490268 http://dx.doi.org/10.3389/fcell.2021.720078 |
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author | Tang, Yu Wu, Qiuyu Gao, Mang Ryu, Esther Pei, Zifei Kissinger, Samuel T. Chen, Yuchen Rao, Abhinav K. Xiang, Zongqin Wang, Tao Li, Wen Chen, Gong Chubykin, Alexander A. |
author_facet | Tang, Yu Wu, Qiuyu Gao, Mang Ryu, Esther Pei, Zifei Kissinger, Samuel T. Chen, Yuchen Rao, Abhinav K. Xiang, Zongqin Wang, Tao Li, Wen Chen, Gong Chubykin, Alexander A. |
author_sort | Tang, Yu |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8416524 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84165242021-09-05 Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy Tang, Yu Wu, Qiuyu Gao, Mang Ryu, Esther Pei, Zifei Kissinger, Samuel T. Chen, Yuchen Rao, Abhinav K. Xiang, Zongqin Wang, Tao Li, Wen Chen, Gong Chubykin, Alexander A. Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2021-08-18 /pmc/articles/PMC8416524/ /pubmed/34490268 http://dx.doi.org/10.3389/fcell.2021.720078 Text en Copyright © 2021 Tang, Wu, Gao, Ryu, Pei, Kissinger, Chen, Rao, Xiang, Wang, Li, Chen and Chubykin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Tang, Yu Wu, Qiuyu Gao, Mang Ryu, Esther Pei, Zifei Kissinger, Samuel T. Chen, Yuchen Rao, Abhinav K. Xiang, Zongqin Wang, Tao Li, Wen Chen, Gong Chubykin, Alexander A. Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy |
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 | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416524/ https://www.ncbi.nlm.nih.gov/pubmed/34490268 http://dx.doi.org/10.3389/fcell.2021.720078 |
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