Homeostatic regulation of perisynaptic MMP9 activity in the amblyopic visual cortex
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
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
- Sacha B Nelson, Brandeis University, United States
Version history
- Received: October 17, 2019
- Accepted: December 19, 2019
- Accepted Manuscript published: December 23, 2019 (version 1)
- 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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