ATLAS: a rationally designed anterograde transsynaptic tracer.
Jacqueline F Rivera1, Haoyang Huang1,2, Weiguang Weng1
1Department of Biological Sciences, Dornsife College, University of Southern California, Los Angeles, CA, USA.
Nature Methods
|May 1, 2025
Summary
Scientists developed ATLAS, a novel protein for anterograde transsynaptic tracing of neural circuits. This new tool maps neuronal connections forward from genetically defined cells, offering a non-toxic and activity-dependent method for studying brain circuitry.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Rabies virus enables retrograde neural circuit mapping from specific cells.
- A lack of comparable tools for anterograde tracing limits comprehensive circuit analysis.
Purpose of the Study:
- To develop a novel method for anterograde transsynaptic tracing from genetically defined neurons.
- To create a tool that enables tracing neural connections in a forward direction.
Main Methods:
- Engineered a protein called ATLAS for anterograde tracing.
- ATLAS induces presynaptic release of a payload containing an antibody-like protein (AMPA.FingR) and a recombinase.
- Payload is endocytosed by postsynaptic cells, delivered to the nucleus, and activates a reporter via recombinase.
Main Results:
- ATLAS successfully mediated monosynaptic transneuronal tracing in mice.
- The tracing was strictly anterograde, synaptic, and non-toxic.
- ATLAS-mediated tracing demonstrated activity dependence, highlighting active circuits.
Conclusions:
- ATLAS provides a new, versatile tool for anterograde neural circuit tracing.
- The modular nature of ATLAS allows for independent modification and future development.
- This method enables the study of active neural circuits underlying specific behaviors.
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