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

Kavli Affiliate: Edward Chang

| Authors: Elisabetta Furlanis, Min Dai, Brenda Leyva Garcia, Josselyn Vergara, Ana Pereira, Kenneth Pelkey, Thien Tran, Bram L. Gorissen, Anna Vlacho, Ariel Hairston, Shuhan Huang, Deepanjali Dwivedi, Sarah Du, Sara Wills, Justin McMahon, Anthony T. Lee, Edward F. Chang, Taha Razzaq, Ahmed Qazi, Geoffrey Vargish, Xiaoqing Yuan, Adam Caccavano, Steven Hunt, Ramesh Chittajallu, Nadiya McLean, Lauren Hewit, 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, Emmie Banks, Viktor Janos Olah, Shovan Naskar, Sophie Hill, Sophie Liebergall, Rohan Badiani, Lili Hyde, Qing Xu, Kathryn C. Allaway, Ethan M. Goldberg, Tomasz J. Nowakowski, Soohyun Lee, Anne E. Takesian, Leena A. Ibrahim, Asim Iqbal, Chris J. McBain, Jordane Dimidschstein, Gord Fishell and Yating Wang

| Summary:

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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