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


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.

SUBMITTER: Furlanis E 

PROVIDER: S-EPMC11291062 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature

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

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

bioRxiv : the preprint server for biology 20250422


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 dis  ...[more]

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