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Related Experiment Video

Updated: Jul 15, 2025

Conditional Genetic Transsynaptic Tracing in the Embryonic Mouse Brain
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ATLAS: A rationally designed anterograde transsynaptic tracer.

Jacqueline F Rivera1,2, Weiguang Weng1,2, Haoyang Huang1,2,3

  • 1Department of Biology, University of Southern California, Los Angeles, CA 90089.

Biorxiv : the Preprint Server for Biology
|September 25, 2023
PubMed
Summary

Researchers developed ATLAS, a novel anterograde transsynaptic tracing method. This non-toxic tool uses an antibody-like sensor to map neural circuits, enabling precise visualization of neuronal connections in the brain.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Neural circuits are fundamental to brain processing.
  • Current retrograde tracing methods, like modified rabies virus, are effective but anterograde tracing lacks reliable, non-toxic tools.
  • Understanding neural circuit connectivity is crucial for neuroscience research.

Purpose of the Study:

  • To develop a novel, reliable, and non-toxic method for anterograde transsynaptic tracing of neural circuits.
  • To enable precise mapping of neuronal connections in the forward direction.
  • To provide a tool for activity-dependent circuit tracing.

Main Methods:

  • Development of ATLAS (Anterograde Transsynaptic Label based on Antibody-like Sensors), utilizing an antibody-like protein (AMPA.FingR) targeting the AMPA receptor subunit GluA1.
  • Engineering ATLAS to release AMPA.FingR and a payload (e.g., Cre recombinase) from presynaptic sites.
  • Testing ATLAS in vivo and in dissociated cultures for efficacy, specificity, and toxicity.

Main Results:

  • ATLAS successfully mediates strictly anterograde, synaptic, and non-toxic monosynaptic tracing from genetically defined cells.
  • The method demonstrates activity dependence, suggesting potential for tracing circuits involved in specific behaviors.
  • Successful application in both in vivo and in vitro model systems.

Conclusions:

  • ATLAS provides a groundbreaking solution for anterograde neural circuit tracing, addressing a significant gap in neuroscience tools.
  • The method's reliability, specificity, and non-toxicity make it a valuable asset for mapping brain connectivity.
  • Activity-dependent tracing capabilities open new avenues for studying dynamic neural circuits and behavior.