Enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits
Authors: Hunker Avery C. , Wirthlin Morgan E. , Gill Gursajan , Johansen Nelson J. , Hooper Marcus , Omstead Victoria , Taskin Naz , Weed Natalie , Vargas Sara , Bendrick Jacqueline L. , Gore Bryan , Ben-Simon Yoav , Bishaw Yeme , Opitz-Araya Ximena , Martinez Refugio A. , Way Sharon , Thyagarajan Bargavi , Lerma M. Nathaly , Laird Will , Sven Otto , Sanchez Raymond E.A. , Alexander Jason R. , Amaya Avalon , Amster Adam , Ayala Angela , Baker Pam M. , Barcelli Tyler , Barta Stuard , Bertagnolli Darren , Bielstein Cameron , Bishwakarma Prajal , Bowlus Jessica , Boyer Gabriella , Brouner Krissy , Casian Brittny , Casper Tamara , Chakka Anish Bhaswanth , Chakrabarty Rushil , Clark Michael , Colbert Kaity , Daniel Scott , Dawe Tim , Departee Maxwell , DiValentin Peter , Donadio Nicholas P. , Dotson Nadezhda I. , Dwivedi Deepanjali , Egdorf Tom , Fliss Tim , Gary Amanda , Goldy Jeff , Grasso Conor , Groce Erin L. , Gudsnuk Kathryn , Han Warren , Haradon Zeb , Hastings Sam , Helback Olivia , Ho Windy V. , Huang Cindy , Johnson Tye , Jones Danielle L. , Juneau Zoe , Kenney Jaimie , Leibly Madison , Li Su , Liang Elizabeth , Loeffler Henry , Lusk Nicholas A. , Madigan Zachary , Malloy Jessica , Malone Jocelin , McCue Rachel , Melchor Jose , Mich John K. , Moosman Skyler , Morin Elyse , Naidoo Robyn , Newman Dakota , Ngo Kiet , Nguyen Katrina , Oster Aaron L. , Ouellette Ben , Oyama Alana A. , Pena Nick , Pham Trangthanh , Phillips Elliot , Pom Christina , Potekhina Lydia , Ransford Shea , Reding Melissa , Rette Dean F. , Reynoldson Cade , Rimorin Christine , Rios Sigler Ana , Rocha Dana B. , Ronellenfitch Kara , Ruiz Augustin , Sawyer Lane , Sevigny Josh , Shapovalova Nadiya V. , Shepard Noah , Shulga Lyudmila , Soliman Sherif , Staats Brian , Taormina Michael J. , Tieu Michael , Wang Yimin , Wilkes Josh , Wood Toren , Zhou Thomas , Williford Ali , Dee Nick , Mollenkopf Tyler , Ng Lydia , Esposito Luke , Kalmbach Brian , Yao Shenqin , Ariza Jeanelle , Mufti Shoaib , Smith Kimberly , Waters Jack , Ersing Ina , Patrick Marcella , Zeng Hongkui , Lein Ed S. , Kojima Yoshiko , Horwitz Greg , Owen Scott F. , Levi Boaz P. , Daigle Tanya L. , Tasic Bosiljka , Bakken Trygve E. , Ting Jonathan T. 
Published: September 2024

AbstractWe present an enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits. Best-in-class vectors were curated for accessing major striatal neuron populations including medium spiny neurons (MSNs), direct and indirect pathway MSNs, as well as Sst-Chodl, Pvalb-Pthlh, and cholinergic interneurons. Specificity was evaluated by multiple modes of molecular validation, three different routes of virus delivery, and with diverse transgene cargos. Importantly, we provide detailed information necessary to achieve reliable cell type specific labeling under different experimental contexts. We demonstrate direct pathway circuit-selective optogenetic perturbation of behavior and multiplex labeling of striatal interneuron types for targeted analysis of cellular features. Lastly, we show conservedin vivoactivity for exemplary MSN enhancers in rat and macaque. This collection of striatal enhancer AAVs offers greater versatility compared to available transgenic lines and can readily be applied for cell type and circuit studies in diverse mammalian species beyond the mouse model.