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Tracing neuronal circuits in transgenic animals by transneuronal control of transcription (TRACT)

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Cite as: eLife 2017;6:e32027 doi: 10.7554/eLife.32027

Abstract

Understanding the computations that take place in brain circuits requires identifying how neurons in those circuits are connected to one another. We describe a technique called TRACT (TRAnsneuronal Control of Transcription) based on ligand-induced intramembrane proteolysis to reveal monosynaptic connections arising from genetically labeled neurons of interest. In this strategy, neurons expressing an artificial ligand ('donor' neurons) bind to and activate a genetically-engineered artificial receptor on their synaptic partners ('receiver' neurons). Upon ligand-receptor binding at synapses the receptor is cleaved in its transmembrane domain and releases a protein fragment that activates transcription in the synaptic partners. Using TRACT in Drosophila we have confirmed the connectivity between olfactory receptor neurons and their postsynaptic targets, and have discovered potential new connections between neurons in the circadian circuit. Our results demonstrate that the TRACT method can be used to investigate the connectivity of neuronal circuits in the brain.

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Author details

  1. Ting-hao Huang

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Peter Niesman

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Deepshika Arasu

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Daniel Lee

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadema, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Aubrie De La Cruz

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Antuca Callejas

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Elizabeth J Hong

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Carlos Lois

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    For correspondence
    clois@caltech.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-7305-2317

Funding

National Institutes of Health (U01MH109147)

  • Carlos Lois

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Mani Ramaswami, Reviewing Editor, Trinity College Dublin, Ireland

Publication history

  1. Received: September 15, 2017
  2. Accepted: December 2, 2017
  3. Accepted Manuscript published: December 12, 2017 (version 1)

Copyright

© 2017, Huang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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