TY - JOUR T1 - Viral manipulation of functionally distinct neurons from mice to humans JF - bioRxiv DO - 10.1101/808170 SP - 808170 AU - Douglas Vormstein-Schneider AU - Jessica Lin AU - Kenneth Pelkey AU - Ramesh Chittajallu AU - Baolin Guo AU - Mario Arias Garcia AU - Kathryn Allaway AU - Sofia Sakopoulos AU - Gates Schneider AU - Olivia Stevenson AU - Josselyn Vergara AU - Jitendra Sharma AU - Qiangge Zhang AU - Tom Franken AU - Jared Smith AU - Leena Ibrahim AU - Kevin Mastro AU - Ehsan Sabri AU - Shuhan Huang AU - Emilia Favuzzi AU - Timothy Burbridge AU - Qing Xu AU - Lihua Guo AU - Ian Vogel AU - Vanessa Sanchez AU - Giuseppe Saldi AU - Xiaoqing Yuan AU - Kareem Zaghloul AU - Orrin Devinsky AU - Bernardo Sabatini AU - Renata Batista-Brito AU - John Reynolds AU - Guoping Feng AU - Zhanyan Fu AU - Chris McBain AU - Gord Fishell AU - Jordane Dimidschstein Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/01/29/808170.abstract N2 - Recent success in identifying gene regulatory elements in the context of recombinant adeno-associated virus vectors have enabled cell type-restricted gene expression. However, within the cerebral cortex these tools are presently limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple novel enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we identified enhancers that target the breadth of its expression, including two that are selective for parvalbumin and vasoactive intestinal peptide cortical interneurons. Demonstrating the functional utility of these elements, we found that the PV-specific enhancer allowed for the selective targeting and manipulation of these neurons across species, from mice to humans. Finally, we demonstrate that our selection method is generalizable to other genes and characterize four additional PV-specific enhancers with exquisite specificity for distinct regions of the brain. Altogether, these viral tools can be used for cell-type specific circuit manipulation and hold considerable promise for use in therapeutic interventions. ER -