An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes.

IF 15 1区医学 Q1 NEUROSCIENCES

Neuron Pub Date : 2025-05-21 DOI:10.1016/j.neuron.2025.05.002

Elisabetta Furlanis, Min Dai, Brenda Leyva Garcia, Thien Tran, Josselyn Vergara, Ana Pereira, Bram L Gorissen, Sara Wills, Anna Vlachos, Ariel Hairston, Deepanjali Dwivedi, Sarah Du, Justin McMahon, Shuhan Huang, Annunziato Morabito, Arenski Vazquez, Soyoun Kim, Anthony T Lee, Edward F Chang, Taha Razzaq, Ahmed Qazi, Geoffrey Vargish, Xiaoqing Yuan, Adam Caccavano, Steven Hunt, Ramesh Chittajallu, Nadiya McLean, Lauren Hewitt, Emily Paranzino, Haley Rice, Alex C Cummins, Anya Plotnikova, Arya Mohanty, Anne Claire Tangen, Jung Hoon Shin, Reza Azadi, Mark A G Eldridge, Veronica A Alvarez, Bruno B Averbeck, Mansour Alyahyay, Tania Reyes Vallejo, Mohammed Soheib, Lucas G Vattino, Cathryn P MacGregor, Carolina Piletti Chatain, Emmie Banks, Viktor Janos Olah, Shovan Naskar, Sophie Hill, Sophie Liebergall, Rohan Badiani, Lili Hyde, Ella Hanley, Qing Xu, Kathryn C Allaway, Ethan M Goldberg, Matthew J M Rowan, Tomasz J Nowakowski, Soohyun Lee, Emilia Favuzzi, Pascal S Kaeser, Lucas Sjulson, Renata Batista-Brito, Anne E Takesian, Leena A Ibrahim, Asim Iqbal, Kenneth A Pelkey, Chris J McBain, Jordane Dimidschstein, Gord Fishell, Yating Wang

{"title":"An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes.","authors":"Elisabetta Furlanis, Min Dai, Brenda Leyva Garcia, Thien Tran, Josselyn Vergara, Ana Pereira, Bram L Gorissen, Sara Wills, Anna Vlachos, Ariel Hairston, Deepanjali Dwivedi, Sarah Du, Justin McMahon, Shuhan Huang, Annunziato Morabito, Arenski Vazquez, Soyoun Kim, Anthony T Lee, Edward F Chang, Taha Razzaq, Ahmed Qazi, Geoffrey Vargish, Xiaoqing Yuan, Adam Caccavano, Steven Hunt, Ramesh Chittajallu, Nadiya McLean, Lauren Hewitt, Emily Paranzino, Haley Rice, Alex C Cummins, Anya Plotnikova, Arya Mohanty, Anne Claire Tangen, Jung Hoon Shin, Reza Azadi, Mark A G Eldridge, Veronica A Alvarez, Bruno B Averbeck, Mansour Alyahyay, Tania Reyes Vallejo, Mohammed Soheib, Lucas G Vattino, Cathryn P MacGregor, Carolina Piletti Chatain, Emmie Banks, Viktor Janos Olah, Shovan Naskar, Sophie Hill, Sophie Liebergall, Rohan Badiani, Lili Hyde, Ella Hanley, Qing Xu, Kathryn C Allaway, Ethan M Goldberg, Matthew J M Rowan, Tomasz J Nowakowski, Soohyun Lee, Emilia Favuzzi, Pascal S Kaeser, Lucas Sjulson, Renata Batista-Brito, Anne E Takesian, Leena A Ibrahim, Asim Iqbal, Kenneth A Pelkey, Chris J McBain, Jordane Dimidschstein, Gord Fishell, Yating Wang","doi":"10.1016/j.neuron.2025.05.002","DOIUrl":null,"url":null,"abstract":"<p><p>In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate specific neuronal subtypes are still limited. Here, we performed systematic analysis of single-cell genomic data to identify enhancer candidates for each of the telencephalic interneuron subtypes. We established a set of enhancer-AAV tools that are highly specific for distinct cortical interneuron populations and striatal cholinergic interneurons. These enhancers, when used in the context of different effectors, can target (fluorescent proteins), observe activity (GCaMP), and manipulate (opto-genetics) specific neuronal subtypes. We also validated our enhancer-AAV tools across species. Thus, we provide the field with a powerful set of tools to study neural circuits and functions and to develop precise and targeted therapy.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":"113 10","pages":"1525-1547.e15"},"PeriodicalIF":15.0000,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuron","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.neuron.2025.05.002","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate specific neuronal subtypes are still limited. Here, we performed systematic analysis of single-cell genomic data to identify enhancer candidates for each of the telencephalic interneuron subtypes. We established a set of enhancer-AAV tools that are highly specific for distinct cortical interneuron populations and striatal cholinergic interneurons. These enhancers, when used in the context of different effectors, can target (fluorescent proteins), observe activity (GCaMP), and manipulate (opto-genetics) specific neuronal subtypes. We also validated our enhancer-AAV tools across species. Thus, we provide the field with a powerful set of tools to study neural circuits and functions and to develop precise and targeted therapy.

查看原文本刊更多论文

一个增强器- aav工具箱，用于靶向和操纵不同的中间神经元亚型。

近年来，我们和其他人已经确定了一些增强子，当纳入rAAV载体时，可以限制转基因在特定神经元群体中的表达。然而，病毒获取和操纵特定神经元亚型的工具仍然有限。在这里，我们对单细胞基因组数据进行了系统分析，以确定每种端脑中间神经元亚型的增强子候选子。我们建立了一套增强- aav工具，对不同的皮质中间神经元群体和纹状体胆碱能中间神经元具有高度特异性。这些增强子，当在不同效应物的背景下使用时，可以靶向（荧光蛋白），观察活性（GCaMP），并操纵（光遗传学）特定的神经元亚型。我们还跨物种验证了我们的增强器- aav工具。因此，我们为该领域提供了一套强大的工具来研究神经回路和功能，并开发精确和靶向治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Neuron 医学-神经科学

CiteScore

24.50

自引率

3.10%

发文量

382

审稿时长

1 months

期刊介绍： Established as a highly influential journal in neuroscience, Neuron is widely relied upon in the field. The editors adopt interdisciplinary strategies, integrating biophysical, cellular, developmental, and molecular approaches alongside a systems approach to sensory, motor, and higher-order cognitive functions. Serving as a premier intellectual forum, Neuron holds a prominent position in the entire neuroscience community.