Andreas Björefeldt, Jeremy Murphy, Emmanuel L Crespo, Gerard G Lambert, Mansi Prakash, Ebenezer C Ikefuama, Nina Friedman, Tariq M Brown, Diane Lipscombe, Christopher I Moore, Ute Hochgeschwender, Nathan C Shaner
{"title":"由 FRET 修饰生物发光驱动的单分子高效光学和化学控制。","authors":"Andreas Björefeldt, Jeremy Murphy, Emmanuel L Crespo, Gerard G Lambert, Mansi Prakash, Ebenezer C Ikefuama, Nina Friedman, Tariq M Brown, Diane Lipscombe, Christopher I Moore, Ute Hochgeschwender, Nathan C Shaner","doi":"10.1117/1.NPh.11.2.021005","DOIUrl":null,"url":null,"abstract":"<p><strong>Significance: </strong>Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a single actuator molecule (a LuMinOpsin, LMO).</p><p><strong>Aim: </strong>To further enhance the utility of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO activation.</p><p><strong>Approach: </strong>We developed novel luciferases optimized for Förster resonance energy transfer when fused to the fluorescent protein mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to <i>Volvox</i> Channelrhodopsin 1 (VChR1).</p><p><strong>Results: </strong>A new LMO generated from this approach (LMO7) showed significantly stronger BL-driven opsin activation compared to previous and other new variants. We extensively benchmarked LMO7 against LMO3 (current standard) and found significantly stronger neuronal activity modulation <i>ex vivo</i> and <i>in vivo</i>, and efficient modulation of behavior.</p><p><strong>Conclusions: </strong>We report a robust new option for achieving multiple modes of control in a single actuator and a promising engineering strategy for continued improvement of BL-OG.</p>","PeriodicalId":54335,"journal":{"name":"Neurophotonics","volume":"11 2","pages":"021005"},"PeriodicalIF":4.8000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917299/pdf/","citationCount":"0","resultStr":"{\"title\":\"Efficient opto- and chemogenetic control in a single molecule driven by FRET-modified bioluminescence.\",\"authors\":\"Andreas Björefeldt, Jeremy Murphy, Emmanuel L Crespo, Gerard G Lambert, Mansi Prakash, Ebenezer C Ikefuama, Nina Friedman, Tariq M Brown, Diane Lipscombe, Christopher I Moore, Ute Hochgeschwender, Nathan C Shaner\",\"doi\":\"10.1117/1.NPh.11.2.021005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Significance: </strong>Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a single actuator molecule (a LuMinOpsin, LMO).</p><p><strong>Aim: </strong>To further enhance the utility of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO activation.</p><p><strong>Approach: </strong>We developed novel luciferases optimized for Förster resonance energy transfer when fused to the fluorescent protein mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to <i>Volvox</i> Channelrhodopsin 1 (VChR1).</p><p><strong>Results: </strong>A new LMO generated from this approach (LMO7) showed significantly stronger BL-driven opsin activation compared to previous and other new variants. We extensively benchmarked LMO7 against LMO3 (current standard) and found significantly stronger neuronal activity modulation <i>ex vivo</i> and <i>in vivo</i>, and efficient modulation of behavior.</p><p><strong>Conclusions: </strong>We report a robust new option for achieving multiple modes of control in a single actuator and a promising engineering strategy for continued improvement of BL-OG.</p>\",\"PeriodicalId\":54335,\"journal\":{\"name\":\"Neurophotonics\",\"volume\":\"11 2\",\"pages\":\"021005\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917299/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurophotonics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1117/1.NPh.11.2.021005\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/3/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurophotonics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1117/1.NPh.11.2.021005","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Efficient opto- and chemogenetic control in a single molecule driven by FRET-modified bioluminescence.
Significance: Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a single actuator molecule (a LuMinOpsin, LMO).
Aim: To further enhance the utility of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO activation.
Approach: We developed novel luciferases optimized for Förster resonance energy transfer when fused to the fluorescent protein mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to Volvox Channelrhodopsin 1 (VChR1).
Results: A new LMO generated from this approach (LMO7) showed significantly stronger BL-driven opsin activation compared to previous and other new variants. We extensively benchmarked LMO7 against LMO3 (current standard) and found significantly stronger neuronal activity modulation ex vivo and in vivo, and efficient modulation of behavior.
Conclusions: We report a robust new option for achieving multiple modes of control in a single actuator and a promising engineering strategy for continued improvement of BL-OG.
期刊介绍：
At the interface of optics and neuroscience, Neurophotonics is a peer-reviewed journal that covers advances in optical technology applicable to study of the brain and their impact on the basic and clinical neuroscience applications.
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