Enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits

作者：Avery C. Hunker, Morgan Wirthlin, Gursajan Gill, Nelson Johansen, Marcus Hooper, Victoria Omstead, Sara Vargas, M. Nathaly Lerma, Naz Taskin, Natalie Weed, William D. Laird, Yemeserach M. Bishaw, Jacqueline L. Bendrick, Bryan B. Gore, Yoav Ben‐Simon, Ximena Opitz-Araya, Refugio A. Martinez, Sharon W. Way, Bargavi Thyagarajan, Sven Otto, Raymond Sanchez, Jason R. Alexander, Avalon Amaya, Adam Amster, Joel Arbuckle, Angela Ayala, Pam M. Baker, Tyler Barcelli, Stuard Barta, Darren Bertagnolli, Cameron Bielstein, Prajal Bishwakarma, Jessica Bowlus, Gabriella Boyer, Krissy Brouner, Brittny Casian, Tamara Casper, Anish Bhaswanth Chakka, Rushil Chakrabarty, Michael Clark, Kaity Colbert, Scott Daniel, Tim Dawe, Maxwell Departee, Peter DiValentin, Nicholas Donadio, Nadezhda Dotson, Deepanjali Dwivedi, Tom Egdorf, Tim Fliss, Amanda Gary, Jeff Goldy, Conor Grasso, Erin L Groce, Kathryn Gudsnuk, Warren Han, Zeb Haradon, Sam Hastings, Olivia Helback, Windy Ho, Cindy Huang, Tye Johnson, Danielle Jones, Zoe Juneau, Jaimie Kenney, Madison Leibly, Li Su, Elizabeth Liang, Henry Loeffler, Nicholas A. Lusk, Zachary Madigan, Jessica R. Malloy, Jocelin Malone, Rachel McCue, Jose Melchor, John K. Mich, Skyler Moosman, Elyse L. Morin, R. Naidoo, Dakota Newman, Kiet Ngo, Katrina Nguyen, Aaron Oster, Ben Ouellette, Alana Oyama, Nick Pena, Trangthanh Pham, Elliot J Phillips, Christina Alice Pom, Lydia Potekhina, Shea Ransford, Melissa Reding, Dean F. Rette, Cade Reynoldson, Christine Rimorin, Ana Rios Sigler, Dana B. Rocha, Kara Ronellenfitch, Augustin Ruiz, Lane Sawyer, Joshua P Sevigny, Nadiya V. Shapovalova, Noah Shepard, Lyudmila Shulga, Sherif Soliman, Brian Staats, Michael J. Taormina, Michael Tieu, Yimin Wang, J. J. Wilkes, Toren Wood, Tingfa Zhou, Ali Williford, Nick Dee, Tyler Mollenkopf, Lydia Ng, Luke Esposito, Brian Kalmbach, Shenqin Yao, Jeanelle Ariza, Forrest Collman, Shoaib Mufti, Kimberly A. Smith, Jack Waters, Ina Ersing, Marcella Patrick, Hongkui Zeng, Ed S. Lein, Yoshiko Kojima, Gregory D. Horwitz, Scott F. Owen, Boaz P. Levi, Tanya L. Daigle, Bosiljka Tasic, Trygve E. Bakken, Jonathan T. Ting · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2024 · DOI：10.1101/2024.09.27.615553 · 被引用次数：14 · 研究领域：Neuroscience and Neural Engineering、Neural dynamics and brain function、Advanced Fluorescence Microscopy Techniques

ABSTRACT We 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 conserved in vivo activity 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.