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Developmental dysregulation of MMP-9 may also lead to neurodevelopmental disorders (ND). Here, we test the hypothesis that chronically elevated MMP-9 activity during early neurodevelopment is responsible for neural circuit hyperconnectivity observed in\n                    <jats:italic>Xenopus<\/jats:italic>\n                    tadpoles after early exposure to valproic acid (VPA), a known teratogen associated with ND in humans. In\n                    <jats:italic>Xenopus<\/jats:italic>\n                    tadpoles, VPA exposure results in excess local synaptic connectivity, disrupted social behavior and increased seizure susceptibility. We found that overexpressing MMP-9 in the brain copies effects of VPA on synaptic connectivity, and blocking MMP-9 activity pharmacologically or genetically reverses effects of VPA on physiology and behavior. We further show that during normal neurodevelopment MMP-9 levels are tightly regulated by neuronal activity and required for structural plasticity. These studies show a critical role for MMP-9 in both normal and abnormal development.\n                  <\/jats:p>","DOI":"10.7554\/elife.62147","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T08:00:15Z","timestamp":1626768015000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.62147","source":"Crossref","is-referenced-by-count":21,"title":["Role of matrix metalloproteinase-9 in neurodevelopmental deficits and experience-dependent plasticity in Xenopus laevis"],"prefix":"10.7554","volume":"10","author":[{"given":"Sayali V","family":"Gore","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Brown University, Providence, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J","family":"James","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Brown University, Providence, United 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