ATLAS: a rationally designed anterograde transsynaptic tracer
Genetically modified rabies virus can map neural circuits retrogradely from genetically determined cells. However, similar tools for anterograde tracing are not available. Here, we describe a method for anterograde transsynaptic tracing from genetically determined neurons based on a rationally designed protein, ATLAS. Expression of ATLAS in neurons causes presynaptic release of a payload composed of an antibody-like protein, AMPA.FingR, which binds to the N terminus of GluA1, and a recombinase. In the synaptic cleft, AMPA.FingR binds to GluA1, causing the payload to be endocytosed into postsynaptic cells and delivered to the nucleus, where it triggers expression of a recombinase-dependent reporter. In mice, ATLAS mediates monosynaptic transneuronal tracing from random or genetically determined cells that is strictly anterograde, synaptic and nontoxic. Moreover, ATLAS-mediated tracing shows activity dependence, suggesting that it can label active circuits underlying specific behaviors. Finally, ATLAS is composed of modular components that can be independently replaced or modified.
Authors
- Ronald F. Paletzki
- Sadhna Rao (ORCID: https://orcid.org/0000-0001-6859-0236)
- Haoyang Huang (ORCID: https://orcid.org/0000-0003-2010-3931)
- Mingli Qin (ORCID: https://orcid.org/0000-0001-5967-5879)
- Scott E. Kanoski (ORCID: https://orcid.org/0000-0001-9526-206X)
- Can Tao (ORCID: https://orcid.org/0000-0002-3914-1877)
- Weiguang Weng
- Jacqueline F. Rivera (ORCID: https://orcid.org/0000-0002-7647-3491)
- Heesung Sohn
- Bernardo L. Sabatini (ORCID: https://orcid.org/0000-0003-0095-9177)
- Charles R. Gerfen (ORCID: https://orcid.org/0000-0001-9008-4882)
- Allison E. Girasole (ORCID: https://orcid.org/0000-0002-1055-9030)
- Li I. Zhang (ORCID: https://orcid.org/0000-0003-0275-8651)
- Bruce E. Herring (ORCID: https://orcid.org/0000-0002-6974-5911)
- Don B. Arnold (ORCID: https://orcid.org/0000-0001-7378-1440)
- Molly E. Klug
- Shun Li (ORCID: https://orcid.org/0000-0002-8580-3843)
- Madeline A Albanese
Institutions
- University of Southern California (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- National Institute of Mental Health (US)
Publication Details
- Journal
- Nature Methods
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1038/s41592-025-02670-x
- Citations
- 7
- Primary Topic
- Photoreceptor and optogenetics research
- Type
- article
- Field-Weighted Citation Impact
- 6.36
Funders
- National Institute of Mental Health
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Neurological Disorders and Stroke