1. Developmental Biology
  2. Neuroscience

Regulation of subcellular dendritic synapse specificity by axon guidance cues

  1. Emily C Sales
  2. Emily L Heckman
  3. Timothy L Warren
  4. Chris Q Doe  Is a corresponding author
  1. Howard Hughes Medical Institute, University of Oregon, United States
https://doi.org/10.7554/eLife.43478
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  1. Emily C Sales
  2. Emily L Heckman
  3. Timothy L Warren
  4. Chris Q Doe
(2019)
Regulation of subcellular dendritic synapse specificity by axon guidance cues
eLife 8:e43478.
https://doi.org/10.7554/eLife.43478
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Abstract

Neural circuit assembly occurs with subcellular precision, yet the mechanisms underlying this precision remain largely unknown. Subcellular synaptic specificity could be achieved by molecularly distinct subcellular domains that locally regulate synapse formation, or by axon guidance cues restricting access to one of several acceptable targets. We address these models using two Drosophila neurons: the dbd sensory neuron and the A08a interneuron. In wild-type larvae, dbd synapses with the A08a medial dendrite but not the A08a lateral dendrite. dbd-specific overexpression of the guidance receptors Unc-5 or Robo-2 results in lateralization of the dbd axon, which forms anatomical and functional monosynaptic connections with the A08a lateral dendrite. We conclude that axon guidance cues, not molecularly distinct dendritic arbors, are a major determinant of dbd-A08a subcellular synapse specificity.

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Code is deposited to the GitHub repository named in the text

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Author details

  1. Emily C Sales

    Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Emily L Heckman

    Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Timothy L Warren

    Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4429-4106

  4. Chris Q Doe

    Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, United States
    For correspondence
    cdoe@uoregon.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5980-8029

Funding

Howard Hughes Medical Institute

  • Chris Q Doe

National Institutes of Health (HD27056)

  • Chris Q Doe

National Institutes of Health (T32HD007348)

  • Emily L Heckman

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

Copyright

© 2019, Sales 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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  1. Emily C Sales
  2. Emily L Heckman
  3. Timothy L Warren
  4. Chris Q Doe
(2019)
Regulation of subcellular dendritic synapse specificity by axon guidance cues
eLife 8:e43478.
https://doi.org/10.7554/eLife.43478

Share this article

https://doi.org/10.7554/eLife.43478

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Further reading

    1. Developmental Biology
    2. Neuroscience

    Presynaptic contact and activity opposingly regulate postsynaptic dendrite outgrowth

    Emily L Heckman, Chris Q Doe
    Research Advance Updated

    The organization of neural circuits determines nervous system function. Variability can arise during neural circuit development (e.g. neurite morphology, axon/dendrite position). To ensure robust nervous system function, mechanisms must exist to accommodate variation in neurite positioning during circuit formation. Previously, we developed a model system in the Drosophila ventral nerve cord to conditionally induce positional variability of a proprioceptive sensory axon terminal, and used this model to show that when we altered the presynaptic position of the sensory neuron, its major postsynaptic interneuron partner modified its dendritic arbor to match the presynaptic contact, resulting in functional synaptic input (Sales et al., 2019). Here, we investigate the cellular mechanisms by which the interneuron dendrites detect and match variation in presynaptic partner location and input strength. We manipulate the presynaptic sensory neuron by (a) ablation; (b) silencing or activation; or (c) altering its location in the neuropil. From these experiments we conclude that there are two opposing mechanisms used to establish functional connectivity in the face of presynaptic variability: presynaptic contact stimulates dendrite outgrowth locally, whereas presynaptic activity inhibits postsynaptic dendrite outgrowth globally. These mechanisms are only active during an early larval critical period for structural plasticity. Collectively, our data provide new insights into dendrite development, identifying mechanisms that allow dendrites to flexibly respond to developmental variability in presynaptic location and input strength.