Santiago R Unda, Lisa E Pomeranz, Roberta Marongiu, Xiaofei Yu, Leah Kelly, Gholamreza Hassanzadeh, Henrik Molina, George Vaisey, Putianqi Wang, Jonathan P Dyke, Edward K Fung, Logan Grosenick, Rick Zirkel, Aldana M Antoniazzi, Sofya Norman, Conor M Liston, Chris Schaffer, Nozomi Nishimura, Sarah A Stanley, Jeffrey M Friedman, Michael G Kaplitt
{"title":"利用磁遗传基因疗法对运动回路进行双向调节。","authors":"Santiago R Unda, Lisa E Pomeranz, Roberta Marongiu, Xiaofei Yu, Leah Kelly, Gholamreza Hassanzadeh, Henrik Molina, George Vaisey, Putianqi Wang, Jonathan P Dyke, Edward K Fung, Logan Grosenick, Rick Zirkel, Aldana M Antoniazzi, Sofya Norman, Conor M Liston, Chris Schaffer, Nozomi Nishimura, Sarah A Stanley, Jeffrey M Friedman, Michael G Kaplitt","doi":"10.1126/sciadv.adp9150","DOIUrl":null,"url":null,"abstract":"<p><p>Here, we report a magnetogenetic system, based on a single anti-ferritin nanobody-TRPV1 receptor fusion protein, which regulated neuronal activity when exposed to magnetic fields. Adeno-associated virus (AAV)-mediated delivery of a floxed nanobody-TRPV1 into the striatum of adenosine-2a receptor-Cre drivers resulted in motor freezing when placed in a magnetic resonance imaging machine or adjacent to a transcranial magnetic stimulation device. Functional imaging and fiber photometry confirmed activation in response to magnetic fields. Expression of the same construct in the striatum of wild-type mice along with a second injection of an AAVretro expressing Cre into the globus pallidus led to similar circuit specificity and motor responses. Last, a mutation was generated to gate chloride and inhibit neuronal activity. Expression of this variant in the subthalamic nucleus in PitX2-Cre parkinsonian mice resulted in reduced <i>c-fos</i> expression and motor rotational behavior. These data demonstrate that magnetogenetic constructs can bidirectionally regulate activity of specific neuronal circuits noninvasively in vivo using clinically available devices.</p>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7000,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463271/pdf/","citationCount":"0","resultStr":"{\"title\":\"Bidirectional regulation of motor circuits using magnetogenetic gene therapy.\",\"authors\":\"Santiago R Unda, Lisa E Pomeranz, Roberta Marongiu, Xiaofei Yu, Leah Kelly, Gholamreza Hassanzadeh, Henrik Molina, George Vaisey, Putianqi Wang, Jonathan P Dyke, Edward K Fung, Logan Grosenick, Rick Zirkel, Aldana M Antoniazzi, Sofya Norman, Conor M Liston, Chris Schaffer, Nozomi Nishimura, Sarah A Stanley, Jeffrey M Friedman, Michael G Kaplitt\",\"doi\":\"10.1126/sciadv.adp9150\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Here, we report a magnetogenetic system, based on a single anti-ferritin nanobody-TRPV1 receptor fusion protein, which regulated neuronal activity when exposed to magnetic fields. Adeno-associated virus (AAV)-mediated delivery of a floxed nanobody-TRPV1 into the striatum of adenosine-2a receptor-Cre drivers resulted in motor freezing when placed in a magnetic resonance imaging machine or adjacent to a transcranial magnetic stimulation device. Functional imaging and fiber photometry confirmed activation in response to magnetic fields. Expression of the same construct in the striatum of wild-type mice along with a second injection of an AAVretro expressing Cre into the globus pallidus led to similar circuit specificity and motor responses. Last, a mutation was generated to gate chloride and inhibit neuronal activity. Expression of this variant in the subthalamic nucleus in PitX2-Cre parkinsonian mice resulted in reduced <i>c-fos</i> expression and motor rotational behavior. These data demonstrate that magnetogenetic constructs can bidirectionally regulate activity of specific neuronal circuits noninvasively in vivo using clinically available devices.</p>\",\"PeriodicalId\":21609,\"journal\":{\"name\":\"Science Advances\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":11.7000,\"publicationDate\":\"2024-10-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463271/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Science Advances\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1126/sciadv.adp9150\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/9 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Advances","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1126/sciadv.adp9150","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/9 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Bidirectional regulation of motor circuits using magnetogenetic gene therapy.
Here, we report a magnetogenetic system, based on a single anti-ferritin nanobody-TRPV1 receptor fusion protein, which regulated neuronal activity when exposed to magnetic fields. Adeno-associated virus (AAV)-mediated delivery of a floxed nanobody-TRPV1 into the striatum of adenosine-2a receptor-Cre drivers resulted in motor freezing when placed in a magnetic resonance imaging machine or adjacent to a transcranial magnetic stimulation device. Functional imaging and fiber photometry confirmed activation in response to magnetic fields. Expression of the same construct in the striatum of wild-type mice along with a second injection of an AAVretro expressing Cre into the globus pallidus led to similar circuit specificity and motor responses. Last, a mutation was generated to gate chloride and inhibit neuronal activity. Expression of this variant in the subthalamic nucleus in PitX2-Cre parkinsonian mice resulted in reduced c-fos expression and motor rotational behavior. These data demonstrate that magnetogenetic constructs can bidirectionally regulate activity of specific neuronal circuits noninvasively in vivo using clinically available devices.
期刊介绍:
Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.