1. Cell Biology
  2. Neuroscience
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Aberrant information transfer interferes with functional axon regeneration

  1. Chen Ding
  2. Marc Hammarlund  Is a corresponding author
  1. Yale University, United States
Research Article
  • Cited 6
  • Views 1,857
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Cite this article as: eLife 2018;7:e38829 doi: 10.7554/eLife.38829

Abstract

Functional axon regeneration requires regenerating neurons to restore appropriate synaptic connectivity and circuit function. To model this process, we developed an assay in C. elegans that links axon and synapse regeneration of a single neuron to recovery of behavior. After axon injury and regeneration of the DA9 neuron, synapses reform at their pre-injury location. However, these regenerated synapses often lack key molecular components. Further, synaptic vesicles accumulate in the dendrite in response to axon injury. Dendritic vesicle release results in information misrouting that suppresses behavioral recovery. Dendritic synapse formation depends on dynein and jnk-1. But even when information transfer is corrected, axonal synapses fail to adequately transmit information. Our study reveals unexpected plasticity during functional regeneration. Regeneration of the axon is not sufficient for the reformation of correct neuronal circuits after injury. Rather, synapse reformation and function are also key variables, and manipulation of circuit reformation improves behavioral recovery.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Chen Ding

    Department of Neuroscience, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Marc Hammarlund

    Department of Neuroscience, Yale University, New Haven, United States
    For correspondence
    marc.hammarlund@yale.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3068-068X

Funding

National Institutes of Health (R01NS094219)

  • Marc Hammarlund

National Institutes of Health (R01NS098817)

  • Marc Hammarlund

China Scholarship Council (CSC-Yale World Scholars in the Biomedical Sciences)

  • Chen Ding

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

Reviewing Editor

  1. Piali Sengupta, Brandeis University, United States

Publication history

  1. Received: May 31, 2018
  2. Accepted: October 26, 2018
  3. Accepted Manuscript published: October 29, 2018 (version 1)
  4. Version of Record published: November 12, 2018 (version 2)

Copyright

© 2018, Ding & Hammarlund

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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