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BIL Logo A Cross-Species Enhancer AAV Toolkit for Cell Type-Specific Targeting Across the Basal Ganglia

[ DOI: https://doi.org/10.35077/g.1193 ]

 

Dataset Citation:
Ting, Jonathan, Bakken, Trygve, Tasic, Bosiljka, Levi, Boaz, Daigle, Tanya. (2026). A Cross-Species Enhancer AAV Toolkit for Cell Type-Specific Targeting Across the Basal Ganglia. [ Collection / Dataset ]. Brain Image Library. https://doi.org/10.35077/g.1193

 

Abstract:
The mammalian basal ganglia (BG) orchestrate diverse motor, cognitive, and affective functions, yet efforts to dissect their cellular circuitry have been limited by a lack of scalable, cell type-specific tools—especially in nonhuman primates. Moreover, key basal ganglia structures outside the striatum, including those critically involved in neuropsychiatric and movement disorders, remain difficult to access due to a lack of high-specificity viral reagents. Here, we present a comprehensive enhancer-AAV library enabling targeted labeling and manipulation of the major neuronal populations across the BG, including striatal projection neuron subtypes, pallidal and subthalamic populations, and dopaminergic and GABAergic midbrain neurons. Using an evolutionarily informed enhancer discovery pipeline, we identified and validated functional enhancers derived from mouse and macaque, including tools for canonical and rare subtypes. Systematic testing revealed robust cross-species activity and highlights both conserved and divergent features of enhancer-driven specificity. Bioinformatic modeling of the full enhancer library identifies key sequence features predictive of tool success, including motif content, chromatin accessibility, and evolutionary conservation. We conclude by identifying cell class-specific enhancer architectures and unique regulatory codes for glial, projection, and interneuron BG lineages. By uniting cross-species enhancer design with deep mechanistic insight, this work establishes the first comprehensive, cross-species viral toolkit for the basal ganglia, unlocking previously inaccessible cell types and setting a new standard for regulatory element-driven circuit targeting.

 

Funding:
National Institutes of Health 1-UF1-MH128339-01 Open-Access AAV Toolbox for Basal Ganglia Cell Types and Circuits;
National Institutes of Health 1-RF1-MH114126-01 Development of tools for cell-type specific labeling of human and mouse neocortical neurons ;
National Institutes of Health 1-R01-NS123959-01 Multimodal analysis of primate infragranular pyramidal neurons and their modulation;
National Institutes of Health 1-UM1-MH130981-01 Functionally guided adult whole brain cell atlas in human and NHP;
Allen Institute for Brain Sciences AIBS-internal Genetic Tools

 

Contributors:
Ting, Jonathan (ProjectLeader) [ORCID: https://orcid.org/0000-0001-8266-0392 ] Allen Institute for Brain Science
Bakken, Trygve (ProjectLeader) [ORCID: https://orcid.org/0000-0003-3373-7386 ] Allen Institute for Brain Science
Tasic, Bosiljka (ProjectLeader) [ORCID: https://orcid.org/0000-0002-6861-4506 ] Allen Institute for Brain Science
Levi, Boaz (ProjectLeader) [ORCID: https://orcid.org/0000-0002-8346-872X ] Allen Institute for Brain Science
Daigle, Tanya (ProjectLeader) [ORCID: https://orcid.org/0000-0001-9700-8452 ] Allen Institute for Brain Science
Hunker, Avery (Researcher) [ORCID: https://orcid.org/0000-0003-0508-3637 ] Allen Institute for Brain Science
Wirthlin, Morgan (Researcher) [ORCID: https://orcid.org/0000-0001-7967-7070 ] Allen Institute for Brain Science
Lerma, M. Nathaly (Researcher) [ORCID: https://orcid.org/0009-0007-8006-9903 ] Allen Institute for Brain Science
Laird, William (Researcher) [ORCID: https://orcid.org/0000-0001-5630-6787 ] Allen Institute for Brain Science
Omstead, Victoria (Researcher) [ORCID: https://orcid.org/0000-0002-3796-970X ] Allen Institute for Brain Science
Taskin, Naz (Researcher) [ORCID: https://orcid.org/0009-0003-2417-8428 ] Allen Institute for Brain Science
Weed, Natalie (Researcher) [ORCID: https://orcid.org/0000-0003-0891-0327 ] Allen Institute for Brain Science
Hooper, Marcus (Researcher) [ORCID: https://orcid.org/0000-0003-1228-5958 ] Allen Institute for Brain Science
Ben-Simon, Yoav (Researcher) [ORCID: https://orcid.org/0000-0002-7075-097X ] Allen Institute for Brain Science
Martinez, Refugio (Researcher) [ORCID: https://orcid.org/0009-0007-3737-3862 ] Allen Institute for Brain Science
Opitz-Araya, Ximena (Researcher) [ORCID: https://orcid.org/0000-0003-4960-3622 ] Allen Institute for Brain Science
Mich, John (Researcher) [ORCID: https://orcid.org/0000-0002-1626-1139 ] Allen Institute for Brain Science
Oster, Aaron (Researcher) [ORCID: https://orcid.org/0000-0002-7074-6444 ] Allen Institute for Brain Science
Dwivedi, Deepanjali (Researcher) [ORCID: https://orcid.org/0000-0001-9992-9167 ] Allen Institute for Brain Science
Groce, Erin (Researcher) [ORCID: https://orcid.org/0009-0008-6357-2774 ] Allen Institute for Brain Science
Thyagarajan, Bargavi (ProjectManager) [ORCID: https://orcid.org/0000-0003-3871-6410 ] Allen Institute for Brain Science
Way, Sharon (ProjectManager) [ORCID: https://orcid.org/0000-0002-9598-2240 ] Allen Institute for Brain Science
Amaya, Avalon (Researcher) [ORCID: https://orcid.org/0000-0003-2274-2892 ] Allen Institute for Brain Science
Alaya, Angela (Researcher) [ORCID: https://orcid.org/0009-0002-8512-6851 ] Allen Institute for Brain Science
Barta, Stuard (Researcher) [ORCID: https://orcid.org/0000-0001-7180-3466 ] Allen Institute for Brain Science
Bertagnolli, Darren (Researcher) [ORCID: https://orcid.org/0000-0002-6626-1567 ] Allen Institute for Brain Science
Pham, Trangthanh (Researcher) [ORCID: https://orcid.org/0000-0002-4738-5062 ] Allen Institute for Brain Science
Casper, Tamara (Researcher) [ORCID: https://orcid.org/0000-0003-1638-3651 ] Allen Institute for Brain Science
Clark, Michael (Researcher) [ORCID: https://orcid.org/0000-0002-8006-4332 ] Allen Institute for Brain Science
Donadio, Nicholas (Researcher) [ORCID: https://orcid.org/0000-0002-6250-1148 ] Allen Institute for Brain Science
Dotson, Nadezhda (Researcher) [ORCID: https://orcid.org/0000-0003-3414-3176 ] Allen Institute for Brain Science
Egdorf, Tom (Researcher) [ORCID: https://orcid.org/0000-0001-9059-8904 ] Allen Institute for Brain Science
Goldy, Jeff (Researcher) [ORCID: https://orcid.org/0000-0001-5140-6922 ] Allen Institute for Brain Science
Grasso, Conor (Researcher) [ORCID: https://orcid.org/0009-0003-6384-4075 ] Allen Institute for Brain Science
Han, Warren (Researcher) [ORCID: https://orcid.org/0009-0006-0104-0380 ] Allen Institute for Brain Science
Hastings, Sam (ProjectManager) [ORCID: https://orcid.org/0009-0008-9107-8597 ] Allen Institute for Brain Science
Ho, Windy (Researcher) [ORCID: https://orcid.org/0000-0001-6200-9906 ] Allen Institute for Brain Science
Johnson, Tye (Researcher) [ORCID: https://orcid.org/0009-0006-7239-7571 ] Allen Institute for Brain Science
Jones, Danielle (Researcher) [ORCID: https://orcid.org/0009-0004-6946-6850 ] Allen Institute for Brain Science
Juneau, Zoe (Researcher) [ORCID: https://orcid.org/0000-0002-8860-5260 ] Allen Institute for Brain Science
Kenney, Jaimie (Researcher) [ORCID: https://orcid.org/0009-0003-5308-2783 ] Allen Institute for Brain Science
Loeffler, Henry (Researcher) [ORCID: https://orcid.org/0009-0007-3935-6863 ] Allen Institute for Brain Science
Lusk, Nicholas (Researcher) [ORCID: https://orcid.org/0000-0001-6346-2083 ] Allen Institute for Brain Science
McCue, Rachel (Researcher) [ORCID: https://orcid.org/0000-0003-4339-7581 ] Allen Institute for Brain Science
Naidoo, Robyn (Researcher) [ORCID: https://orcid.org/0009-0004-0996-8808 ] Allen Institute for Brain Science
Newman, Dakota (Researcher) [ORCID: https://orcid.org/0000-0002-3835-0853 ] Allen Institute for Brain Science
Ngo, Kiet (Researcher) [ORCID: https://orcid.org/0009-0002-5548-1983 ] Allen Institute for Brain Science
Nguyen, Katrina (Researcher) [ORCID: https://orcid.org/0009-0009-8547-9703 ] Allen Institute for Brain Science
Otto, Sven (Researcher) [ORCID: https://orcid.org/0009-0002-8383-4272 ] Allen Institute for Brain Science
Ouellette, Ben (Researcher) [ORCID: https://orcid.org/0000-0003-4913-554X ] Allen Institute for Brain Science
Oyama, Alana (Researcher) [ORCID: https://orcid.org/0000-0002-4492-0533 ] Allen Institute for Brain Science
Phillips, Elliot (Researcher) [ORCID: https://orcid.org/0009-0008-2762-6608 ] Allen Institute for Brain Science
Pom, Christina (Researcher) [ORCID: https://orcid.org/0000-0001-9057-040X ] Allen Institute for Brain Science
Potekhina, Lydia (Researcher) [ORCID: https://orcid.org/0000-0001-8879-7920 ] Allen Institute for Brain Science
Ransford, Shea (Researcher) [ORCID: https://orcid.org/0000-0001-6093-0806 ] Allen Institute for Brain Science
Rimorin, Christine (Researcher) [ORCID: https://orcid.org/0000-0003-1491-8552 ] Allen Institute for Brain Science
Rocha, Dana (Researcher) [ORCID: https://orcid.org/0009-0001-2121-8899 ] Allen Institute for Brain Science
Ruiz, Augustin (Researcher) [ORCID: https://orcid.org/0000-0002-8361-5152 ] Allen Institute for Brain Science
Sanchez, Raymond (ProjectManager) [ORCID: https://orcid.org/0000-0001-9141-090X ] Allen Institute for Brain Science
Taormina, Michael (Researcher) [ORCID: https://orcid.org/0000-0003-4634-4039 ] Allen Institute for Brain Science
Tieu, Michael (Researcher) [ORCID: https://orcid.org/0000-0001-9286-5623 ] Allen Institute for Brain Science
Wilkes, Josh (Researcher) [ORCID: https://orcid.org/0009-0005-4858-2219 ] Allen Institute for Brain Science
Ariza, Jeanelle (Researcher) [ORCID: https://orcid.org/0000-0002-0829-7887 ] Allen Institute for Brain Science
Bhaswanth Chakka, Anish (Researcher) [ORCID: https://orcid.org/0000-0002-1095-1817 ] Allen Institute for Brain Science
Collman, Forrest (ProjectLeader) [ORCID: https://orcid.org/0000-0002-0280-7022 ] Allen Institute for Brain Science
Dee, Nick (ProjectLeader) [ORCID: https://orcid.org/0000-0002-2831-9254 ] Allen Institute for Brain Science
Johansen, Nelson (Researcher) [ORCID: https://orcid.org/0000-0002-4436-969X ] Allen Institute for Brain Science
Mollenkopf, Tyler (ProjectLeader) [ORCID: https://orcid.org/0000-0002-2899-2879 ] Allen Institute for Brain Science
Shapovalova, Nadiya (Researcher) [ORCID: https://orcid.org/0000-0002-8618-8272 ] Allen Institute for Brain Science
Smith, Kimberly (Researcher) [ORCID: https://orcid.org/0000-0002-3142-1970 ] Allen Institute for Brain Science
Waters, Jack (Researcher) [ORCID: https://orcid.org/0000-0002-2312-4183 ] Allen Institute for Brain Science
Williford, Ali (Researcher) [ORCID: https://orcid.org/0009-0000-7282-7515 ] Allen Institute for Brain Science
Yao, Shenqin (Researcher) [ORCID: https://orcid.org/0000-0003-2992-4752 ] Allen Institute for Brain Science
Zeng, Hongkui (ProjectLeader) [ORCID: https://orcid.org/0000-0002-0326-5878 ] Allen Institute for Brain Science
Lein, Ed (ProjectLeader) [ORCID: https://orcid.org/0000-0001-9012-6552 ] Allen Institute for Brain Science

 

Related Identifiers:
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