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Related Experiment Video

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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
PubMed
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.

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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.