Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans

Autor: Douglas Vormstein-Schneider, John V. Reynolds, Zhanyan Fu, Xiaoqing Yuan, Qiangge Zhang, Jared B. Smith, Giuseppe A. Saldi, Vanessa Sanchez, Jitendra Sharma, Gates Schneider, Renata Batista-Brito, Josselyn Vergara, Kareem A. Zaghloul, Jessica Lin, Orrin Devinsky, Timothy Burbridge, Kathryn C. Allaway, Leena A. Ibrahim, Sofia Sakopoulos, Guoping Feng, Emilia Favuzzi, Jordane Dimidschstein, Bram L. Gorissen, Tom P. Franken, Baolin Guo, Gord Fishell, Mario A. Arias-Garcia, Shuhan Huang, Bernardo L. Sabatini, Ramesh Chittajallu, Olivia Stevenson, Kenneth A. Pelkey, Chris J. McBain, Ian Vogel, Qing Xu, Ehsan Sabri, Lihua Guo, Kevin J. M astro
Rok vydání: 2020
Předmět:
Zdroj: Nature Neuroscience. 23:1629-1636
ISSN: 1546-1726
1097-6256
Popis: Recent success in identifying gene-regulatory elements in the context of recombinant adeno-associated virus vectors has enabled cell-type-restricted gene expression. However, within the cerebral cortex these tools are largely limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple new enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we discovered enhancers selective for parvalbumin (PV) and vasoactive intestinal peptide-expressing interneurons. Demonstrating the functional utility of these elements, we show that the PV-specific enhancer allowed for the selective targeting and manipulation of these neurons across vertebrate species, including humans. Finally, we demonstrate that our selection method is generalizable and characterizes additional PV-specific enhancers with exquisite specificity within distinct brain regions. Altogether, these viral tools can be used for cell-type-specific circuit manipulation and hold considerable promise for use in therapeutic interventions.
Databáze: OpenAIRE
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