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Previously we showed that perisynaptic proteolysis by MMP9 mediates the enhancement of plasticity by LRx in binocular adult mice (Murase et al., 2017). However, it was 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 extracellular matrix (ECM) degradation in deprived and non-deprived V1. Indeed, LRx restricted to the amblyopic eye is sufficient to induce 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 the MMP2\/9 activation threshold by DE enables visual input from the amblyopic pathway to trigger robust perisynaptic proteolysis.<\/jats:p>","DOI":"10.7554\/elife.52503","type":"journal-article","created":{"date-parts":[[2019,12,21]],"date-time":"2019-12-21T08:00:20Z","timestamp":1576915220000},"source":"Crossref","is-referenced-by-count":25,"title":["Homeostatic regulation of perisynaptic matrix metalloproteinase 9 (MMP9) activity in the amblyopic visual cortex"],"prefix":"10.7554","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9078-0471","authenticated-orcid":true,"given":"Sachiko","family":"Murase","sequence":"first","affiliation":[{"name":"Department of Biology, University of Maryland, College Park, United States"},{"name":"Neuroscience Cognitive Sciences Program, University of Maryland, College Park, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Winkowski","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Maryland, College Park, United States"},{"name":"Neuroscience Cognitive Sciences Program, University of Maryland, College Park, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Maryland, College Park, United States"},{"name":"Neuroscience Cognitive Sciences Program, University of Maryland, College Park, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7529-5435","authenticated-orcid":true,"given":"Patrick O","family":"Kanold","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Maryland, College Park, United States"},{"name":"Neuroscience Cognitive Sciences Program, University of 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