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Previously, we showed that elevated levels of matrix metalloproteinase\u20109 (MMP\u20109) may contribute to abnormal development of parvalbumin (PV) interneurons and perineuronal nets (PNNs) in the developing auditory cortex (AC) of <jats:italic>Fmr1<\/jats:italic> knock\u2010out (KO) mice, which likely underlie auditory hypersensitivity. Thus, MMP\u20109 may serve as a potential target for treatment of auditory hypersensitivity in FXS. Here, we used the MMP\u20102\/9 inhibitor, SB\u20103CT, to pharmacologically inhibit MMP\u20109 activity during a specific developmental period and to test whether inhibition of MMP\u20109 activity reverses neural oscillation deficits and behavioral impairments by enhancing PNN formation around PV cells in <jats:italic>Fmr1<\/jats:italic> KO mice. Electroencephalography (EEG) was used to measure resting state and sound\u2010evoked electrocortical activity in auditory and frontal cortices of postnatal day (P)22\u201323 male mice before and one\u2010day after treatment with SB\u20103CT (25\u00a0mg\/kg) or vehicle. At P27\u201028, animal behaviors were tested to measure the effects of the treatment on anxiety and hyperactivity. Results show that acute inhibition of MMP\u20109 activity improved evoked synchronization to auditory stimuli and ameliorated mouse behavioral deficits. MMP\u20109 inhibition enhanced PNN formation, increased PV levels and TrkB phosphorylation yet reduced Akt phosphorylation in the AC of <jats:italic>Fmr1<\/jats:italic> KO mice. Our results show that MMP\u20109 inhibition during early postnatal development is beneficial in reducing some auditory processing deficits in the FXS mouse model and may serve as a candidate therapeutic for reversing sensory hypersensitivity in FXS and possibly other ASDs.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15037-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15037","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T21:00:31Z","timestamp":1588798831000},"page":"538-558","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Acute pharmacological inhibition of matrix metalloproteinase\u20109 activity during development restores perineuronal net formation and normalizes auditory processing in <i>Fmr1<\/i> KO mice"],"prefix":"10.1111","volume":"155","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8733-7447","authenticated-orcid":false,"given":"Patricia S.","family":"Pirbhoy","sequence":"first","affiliation":[{"name":"Division of Biomedical Sciences School of Medicine University of California Riverside CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maham","family":"Rais","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences School of Medicine University of California Riverside CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5734-6801","authenticated-orcid":false,"given":"Jonathan W.","family":"Lovelace","sequence":"additional","affiliation":[{"name":"Department of Psychology University of California Riverside Riverside CA 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