Suppression of epileptic seizures by transcranial activation of K+-selective channelrhodopsin
Abstract Optogenetics is a valuable tool for studying the mechanisms of neurological diseases and is now being developed for therapeutic applications. In rodents and macaques, improved channelrhodopsins have been applied to achieve transcranial optogenetic stimulation. While transcranial photoexcita...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-55818-w |
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| author | Xiaodong Duan Chong Zhang Yujie Wu Jun Ju Zhe Xu Xuanyi Li Yao Liu Schugofa Ohdah Oana M. Constantin Yifan Pan Zhonghua Lu Cheng Wang Xiaojing Chen Christine E. Gee Georg Nagel Sheng-Tao Hou Shiqiang Gao Kun Song |
| author_facet | Xiaodong Duan Chong Zhang Yujie Wu Jun Ju Zhe Xu Xuanyi Li Yao Liu Schugofa Ohdah Oana M. Constantin Yifan Pan Zhonghua Lu Cheng Wang Xiaojing Chen Christine E. Gee Georg Nagel Sheng-Tao Hou Shiqiang Gao Kun Song |
| author_sort | Xiaodong Duan |
| collection | DOAJ |
| description | Abstract Optogenetics is a valuable tool for studying the mechanisms of neurological diseases and is now being developed for therapeutic applications. In rodents and macaques, improved channelrhodopsins have been applied to achieve transcranial optogenetic stimulation. While transcranial photoexcitation of neurons has been achieved, noninvasive optogenetic inhibition for treating hyperexcitability-induced neurological disorders has remained elusive. There is a critical need for effective inhibitory optogenetic tools that are highly light-sensitive and capable of suppressing neuronal activity in deep brain tissue. In this study, we developed a highly sensitive moderately K+-selective channelrhodopsin (HcKCR1-hs) by molecular engineering of the recently discovered Hyphochytrium catenoides kalium (potassium) channelrhodopsin 1. Transcranial activation of HcKCR1-hs significantly prolongs the time to the first seizure, increases survival, and decreases seizure activity in several status epilepticus mouse models. Our approach for transcranial optogenetic inhibition of neural hyperactivity may be adapted for cell type-specific neuromodulation in both basic and preclinical settings. |
| format | Article |
| id | doaj-art-0335afc75666422b9891289d8a1b31de |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-0335afc75666422b9891289d8a1b31de2025-01-12T12:31:05ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-025-55818-wSuppression of epileptic seizures by transcranial activation of K+-selective channelrhodopsinXiaodong Duan0Chong Zhang1Yujie Wu2Jun Ju3Zhe Xu4Xuanyi Li5Yao Liu6Schugofa Ohdah7Oana M. Constantin8Yifan Pan9Zhonghua Lu10Cheng Wang11Xiaojing Chen12Christine E. Gee13Georg Nagel14Sheng-Tao Hou15Shiqiang Gao16Kun Song17Shenzhen Key Laboratory of Gene Regulation and Systems Biology, and Brain Research Center, Department of Neuroscience, School of Life Sciences, Southern University of Science and TechnologyDepartment of Neurophysiology, Institute of Physiology, University WürzburgShenzhen Key Laboratory of Gene Regulation and Systems Biology, and Brain Research Center, Department of Neuroscience, School of Life Sciences, Southern University of Science and TechnologyShenzhen Key Laboratory of Gene Regulation and Systems Biology, and Brain Research Center, Department of Neuroscience, School of Life Sciences, Southern University of Science and TechnologyShenzhen Key Laboratory of Gene Regulation and Systems Biology, and Brain Research Center, Department of Neuroscience, School of Life Sciences, Southern University of Science and TechnologyShenzhen Key Laboratory of Gene Regulation and Systems Biology, and Brain Research Center, Department of Neuroscience, School of Life Sciences, Southern University of Science and TechnologyShenzhen Key Laboratory of Gene Regulation and Systems Biology, and Brain Research Center, Department of Neuroscience, School of Life Sciences, Southern University of Science and TechnologyInstitute for Synaptic Neuroscience, University Medical Center Hamburg EppendorfInstitute for Synaptic Neuroscience, University Medical Center Hamburg EppendorfShenzhen Key Laboratory of Gene Regulation and Systems Biology, and Brain Research Center, Department of Neuroscience, School of Life Sciences, Southern University of Science and TechnologyResearch Center for Primate Neuromodulation and Neuroimaging, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesShenzhen Institute of Advanced Technology, Chinese Academy of SciencesShenzhen Key Laboratory of Gene Regulation and Systems Biology, and Brain Research Center, Department of Neuroscience, School of Life Sciences, Southern University of Science and TechnologyInstitute for Synaptic Neuroscience, University Medical Center Hamburg EppendorfDepartment of Neurophysiology, Institute of Physiology, University WürzburgShenzhen Key Laboratory of Gene Regulation and Systems Biology, and Brain Research Center, Department of Neuroscience, School of Life Sciences, Southern University of Science and TechnologyDepartment of Neurophysiology, Institute of Physiology, University WürzburgShenzhen Key Laboratory of Gene Regulation and Systems Biology, and Brain Research Center, Department of Neuroscience, School of Life Sciences, Southern University of Science and TechnologyAbstract Optogenetics is a valuable tool for studying the mechanisms of neurological diseases and is now being developed for therapeutic applications. In rodents and macaques, improved channelrhodopsins have been applied to achieve transcranial optogenetic stimulation. While transcranial photoexcitation of neurons has been achieved, noninvasive optogenetic inhibition for treating hyperexcitability-induced neurological disorders has remained elusive. There is a critical need for effective inhibitory optogenetic tools that are highly light-sensitive and capable of suppressing neuronal activity in deep brain tissue. In this study, we developed a highly sensitive moderately K+-selective channelrhodopsin (HcKCR1-hs) by molecular engineering of the recently discovered Hyphochytrium catenoides kalium (potassium) channelrhodopsin 1. Transcranial activation of HcKCR1-hs significantly prolongs the time to the first seizure, increases survival, and decreases seizure activity in several status epilepticus mouse models. Our approach for transcranial optogenetic inhibition of neural hyperactivity may be adapted for cell type-specific neuromodulation in both basic and preclinical settings.https://doi.org/10.1038/s41467-025-55818-w |
| spellingShingle | Xiaodong Duan Chong Zhang Yujie Wu Jun Ju Zhe Xu Xuanyi Li Yao Liu Schugofa Ohdah Oana M. Constantin Yifan Pan Zhonghua Lu Cheng Wang Xiaojing Chen Christine E. Gee Georg Nagel Sheng-Tao Hou Shiqiang Gao Kun Song Suppression of epileptic seizures by transcranial activation of K+-selective channelrhodopsin Nature Communications |
| title | Suppression of epileptic seizures by transcranial activation of K+-selective channelrhodopsin |
| title_full | Suppression of epileptic seizures by transcranial activation of K+-selective channelrhodopsin |
| title_fullStr | Suppression of epileptic seizures by transcranial activation of K+-selective channelrhodopsin |
| title_full_unstemmed | Suppression of epileptic seizures by transcranial activation of K+-selective channelrhodopsin |
| title_short | Suppression of epileptic seizures by transcranial activation of K+-selective channelrhodopsin |
| title_sort | suppression of epileptic seizures by transcranial activation of k selective channelrhodopsin |
| url | https://doi.org/10.1038/s41467-025-55818-w |
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