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Distinct stages of synapse elimination are induced by burst firing of CA1 neurons and differentially require MEF2A/D

  1. Chia-Wei Chang
  2. Julia Wilkerson
  3. Carly Hale
  4. Jay R Gibson
  5. Kimberly M Huber Is a corresponding author
  1. The University of Texas Southwestern Medical Center, United States
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Cite as: eLife 2017;6:e26278 doi: 10.7554/eLife.26278

Abstract

Experience and activity refine cortical circuits through synapse elimination, but little is known about the activity patterns and downstream molecular mechanisms that mediate this process. We used optogenetics to drive individual mouse CA1 hippocampal neurons to fire in theta frequency bursts to understand how cell autonomous, postsynaptic activity leads to synapse elimination. Brief (1hr) periods of postsynaptic bursting selectively depressed AMPA receptor (R) synaptic transmission, or silenced excitatory synapses, whereas more prolonged (24 hr) firing depressed both AMPAR and NMDAR EPSCs and eliminated spines, indicative of a synapse elimination. Both synapse silencing and elimination required de novo transcription, but only silencing required the activity-dependent transcription factors MEF2A/D. Burst firing induced MEF2A/D-dependent induction of the target gene Arc which contributed to synapse silencing and elimination. This work reveals new and distinct forms of activity-dependent synapse depression and suggests that these processes can occur independently.

Article and author information

Author details

  1. Chia-Wei Chang

    Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-1011-6870
  2. Julia Wilkerson

    Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Carly Hale

    Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jay R Gibson

    Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Kimberly M Huber

    Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    kimberly.huber@utsouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-7479-0661

Funding

Simons Foundation

  • Chia-Wei Chang

National Institutes of Health

  • Chia-Wei Chang
  • Julia Wilkerson
  • Carly Hale
  • Jay R Gibson
  • Kimberly M Huber

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

Ethics

Animal experimentation: All experimental protocols involving mice were performed in accordance with the guidelines and regulations set forth by the Institutional Animal Care and Use Committee at The University of Texas Southwestern Medical Center.

Reviewing Editor

  1. Anne E West, Reviewing Editor, Duke University School of Medicine, United States

Publication history

  1. Received: February 23, 2017
  2. Accepted: September 5, 2017
  3. Accepted Manuscript published: September 13, 2017 (version 1)

Copyright

© 2017, Chang 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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