Homeostatic regulation of perisynaptic MMP9 activity in the amblyopic visual cortex

  1. Sachiko Murase  Is a corresponding author
  2. Dan Winkowski
  3. Ji Liu
  4. Patrick O Kanold
  5. Elizabeth M Quinlan  Is a corresponding author
  1. University of Maryland, United States

Abstract

Dark exposure (DE) followed by light reintroduction (LRx) reactivates robust synaptic plasticity in adult mouse V1, which allows recovery from amblyopia. Previously we showed that LRx-induced perisynaptic proteolysis of extracellular matrix (ECM) by MMP9 mediates the enhanced plasticity in binocular adult mice (Murase et al., 2017). However, it is unknown if a visual system compromised by amblyopia could engage this pathway. Here we show that LRx to adult amblyopic mice induces perisynaptic MMP2/9 activity and ECM degradation in the deprived and non-deprived V1. LRx restricted to the amblyopic eye induces equally robust MMP2/9 activity at thalamo-cortical synapses and ECM degradation in deprived V1. Two-photon live imaging demonstrates that the history of visual experience regulates MMP2/9 activity in V1, and that DE lowers the threshold for the proteinase activation. The homeostatic reduction of MMP2/9 activation threshold by DE enables the visual input from the amblyopic pathway to trigger robust perisynaptic proteolysis.

Data availability

All data generated/analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1-5.

Article and author information

Author details

  1. Sachiko Murase

    Department of Biology, University of Maryland, College Park, United States
    For correspondence
    smurase@umd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9078-0471
  2. Dan Winkowski

    Department of Biology, University of Maryland, College Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ji Liu

    Department of Biology, University of Maryland, College Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Patrick O Kanold

    Department of Biology, University of Maryland, College Park, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7529-5435
  5. Elizabeth M Quinlan

    Department of Biology, University of Maryland, College Park, United States
    For correspondence
    equinlan@umd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3496-6607

Funding

National Eye Institute (R01EY016431)

  • Elizabeth M Quinlan

National Institute on Deafness and Other Communication Disorders (R01DC009607)

  • Patrick O Kanold

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 procedures, under Quinlan lab protocol R-MAY-18-25, conformed to the guidelines of the University of Maryland Institutional Animal Care and Use Committee and the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.

Reviewing Editor

  1. Sacha B Nelson, Brandeis University, United States

Publication history

  1. Received: October 17, 2019
  2. Accepted: December 19, 2019
  3. Accepted Manuscript published: December 23, 2019 (version 1)
  4. Version of Record published: January 15, 2020 (version 2)

Copyright

© 2019, Murase 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. Sachiko Murase
  2. Dan Winkowski
  3. Ji Liu
  4. Patrick O Kanold
  5. Elizabeth M Quinlan
(2019)
Homeostatic regulation of perisynaptic MMP9 activity in the amblyopic visual cortex
eLife 8:e52503.
https://doi.org/10.7554/eLife.52503

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