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

增强子-AAV 工具箱,用于靶向和操纵不同的中间神经元亚型

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作者:Elisabetta Furlanis, Min Dai, Brenda Leyva Garcia, Josselyn Vergara, Ana Pereira, Kenneth Pelkey, Thien Tran, Bram L Gorissen, Anna Vlachos, Ariel Hairston, Shuhan Huang, Deepanjali Dwivedi, Sarah Du, Sara Wills, Justin McMahon, Anthony T Lee, Edward F Chang, Taha Razzaq, Ahmed Qazi, Geoffrey Vargis

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 fine neuronal subtypes are still limited. Here, we performed systematic analysis of single cell genomic data to identify enhancer candidates for each of the cortical interneuron subtypes. We established a set of enhancer-AAV tools that are highly specific for distinct cortical interneuron populations and striatal cholinergic neurons. These enhancers, when used in the context of different effectors, can target (fluorescent proteins), observe activity (GCaMP) and manipulate (opto- or chemo-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.

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