Hunker Avery C, Wirthlin Morgan E, Gill Gursajan, Johansen Nelson J, Hooper Marcus, Omstead Victoria, Vargas Sara, Lerma M Nathaly, Taskin Naz, Weed Natalie, Laird William D, Bishaw Yemeserach M, Bendrick Jacqueline L, Gore Bryan B, Ben-Simon Yoav, Opitz-Araya Ximena, Martinez Refugio A, Way Sharon W, Thyagarajan Bargavi, Otto Sven, Sanchez Raymond E A, Alexander Jason R, Amaya Avalon, Amster Adam, Arbuckle Joel, 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, Chong Peter, 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, Ray Patrick L, Reding Melissa, Rette Dean F, Reynoldson Cade, Rimorin Christine, Sigler Ana Rios, Rocha Dana B, Ronellenfitch Kara, Ruiz Augustin, Sawyer Lane, Sevigny Josh P, 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 E, Yao Shenqin, Ariza Jeanelle, Collman Forrest, 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
Allen Institute for Brain Science, Seattle, WA, USA.
Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
Neuron. 2025 May 21;113(10):1507-1524.e17. doi: 10.1016/j.neuron.2025.04.035.
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, Sst-Chodl, Pvalb-Pthlh, and cholinergic interneurons. Specificity was evaluated by multiple modes of molecular validation, by 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 rats and macaques. 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.
我们展示了一个用于访问和扰动纹状体细胞类型及回路的增强子-腺相关病毒（enhancer-AAV）工具箱。精心挑选了一流的载体，以访问主要的纹状体神经元群体，包括中等棘状神经元（MSN）、直接通路和间接通路的MSN、Sst-Chodl、Pvalb-Pthlh和胆碱能中间神经元。通过多种分子验证模式、三种不同的病毒递送途径以及不同的转基因货物来评估特异性。重要的是，我们提供了在不同实验背景下实现可靠的细胞类型特异性标记所需的详细信息。我们展示了对行为的直接通路电路选择性光遗传学扰动以及对纹状体中间神经元类型的多重标记，用于细胞特征的靶向分析。最后，我们展示了大鼠和猕猴中示例性MSN增强子在体内的保守活性。与现有的转基因品系相比，这个纹状体增强子AAV集合具有更大的通用性，并且可以很容易地应用于小鼠模型以外的多种哺乳动物物种的细胞类型和回路研究。
