An intein-split transactivator for intersectional neural imaging and optogenetic manipulation
Abstract The cell-type-specific recording and manipulation is instrumental to disentangle causal neural mechanisms in physiology and behavior and increasingly requires intersectional control; however, current approaches are largely limited by the number of intersectional features, incompatibility of...
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Nature Portfolio
2022-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-022-31255-x |
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| author | Hao-Shan Chen Xiao-Long Zhang Rong-Rong Yang Guang-Ling Wang Xin-Yue Zhu Yuan-Fang Xu Dan-Yang Wang Na Zhang Shou Qiu Li-Jie Zhan Zhi-Ming Shen Xiao-Hong Xu Gang Long Chun Xu |
| author_facet | Hao-Shan Chen Xiao-Long Zhang Rong-Rong Yang Guang-Ling Wang Xin-Yue Zhu Yuan-Fang Xu Dan-Yang Wang Na Zhang Shou Qiu Li-Jie Zhan Zhi-Ming Shen Xiao-Hong Xu Gang Long Chun Xu |
| author_sort | Hao-Shan Chen |
| collection | DOAJ |
| description | Abstract The cell-type-specific recording and manipulation is instrumental to disentangle causal neural mechanisms in physiology and behavior and increasingly requires intersectional control; however, current approaches are largely limited by the number of intersectional features, incompatibility of common effectors and insufficient gene expression. Here, we utilized the protein-splicing technique mediated by intervening sequences (intein) and devised an intein-based intersectional synthesis of transactivator (IBIST) to selectively control gene expression of common effectors in multiple-feature defined cell types in mice. We validated the specificity and sufficiency of IBIST to control fluorophores, optogenetic opsins and Ca2+ indicators in various intersectional conditions. The IBIST-based Ca2+ imaging showed that the IBIST can intersect five features and that hippocampal neurons tune differently to distinct emotional stimuli depending on the pattern of projection targets. Collectively, the IBIST multiplexes the capability to intersect cell-type features and controls common effectors to effectively regulate gene expression, monitor and manipulate neural activities. |
| format | Article |
| id | doaj-art-cf700a61d9b140b2ad7aca1c96ccff4e |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-cf700a61d9b140b2ad7aca1c96ccff4e2025-01-12T12:29:23ZengNature PortfolioNature Communications2041-17232022-06-0113111410.1038/s41467-022-31255-xAn intein-split transactivator for intersectional neural imaging and optogenetic manipulationHao-Shan Chen0Xiao-Long Zhang1Rong-Rong Yang2Guang-Ling Wang3Xin-Yue Zhu4Yuan-Fang Xu5Dan-Yang Wang6Na Zhang7Shou Qiu8Li-Jie Zhan9Zhi-Ming Shen10Xiao-Hong Xu11Gang Long12Chun Xu13Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesUniversity of the Chinese Academy of SciencesInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesInstitut Pasteur of Shanghai, Chinese Academy of SciencesInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesAbstract The cell-type-specific recording and manipulation is instrumental to disentangle causal neural mechanisms in physiology and behavior and increasingly requires intersectional control; however, current approaches are largely limited by the number of intersectional features, incompatibility of common effectors and insufficient gene expression. Here, we utilized the protein-splicing technique mediated by intervening sequences (intein) and devised an intein-based intersectional synthesis of transactivator (IBIST) to selectively control gene expression of common effectors in multiple-feature defined cell types in mice. We validated the specificity and sufficiency of IBIST to control fluorophores, optogenetic opsins and Ca2+ indicators in various intersectional conditions. The IBIST-based Ca2+ imaging showed that the IBIST can intersect five features and that hippocampal neurons tune differently to distinct emotional stimuli depending on the pattern of projection targets. Collectively, the IBIST multiplexes the capability to intersect cell-type features and controls common effectors to effectively regulate gene expression, monitor and manipulate neural activities.https://doi.org/10.1038/s41467-022-31255-x |
| spellingShingle | Hao-Shan Chen Xiao-Long Zhang Rong-Rong Yang Guang-Ling Wang Xin-Yue Zhu Yuan-Fang Xu Dan-Yang Wang Na Zhang Shou Qiu Li-Jie Zhan Zhi-Ming Shen Xiao-Hong Xu Gang Long Chun Xu An intein-split transactivator for intersectional neural imaging and optogenetic manipulation Nature Communications |
| title | An intein-split transactivator for intersectional neural imaging and optogenetic manipulation |
| title_full | An intein-split transactivator for intersectional neural imaging and optogenetic manipulation |
| title_fullStr | An intein-split transactivator for intersectional neural imaging and optogenetic manipulation |
| title_full_unstemmed | An intein-split transactivator for intersectional neural imaging and optogenetic manipulation |
| title_short | An intein-split transactivator for intersectional neural imaging and optogenetic manipulation |
| title_sort | intein split transactivator for intersectional neural imaging and optogenetic manipulation |
| url | https://doi.org/10.1038/s41467-022-31255-x |
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