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The proteoglycan aggrecan is a core component of the condensed ECM structures termed perineuronal nets (PNNs), and the specific role of PNNs on neural plasticity remains elusive. Here, we genetically targeted the<jats:italic>Acan<\/jats:italic>gene encoding for aggrecan using a novel animal model. This allowed for conditional and targeted loss of aggrecan<jats:italic>in vivo<\/jats:italic>, which ablated the PNN structure and caused a shift in the population of parvalbumin-expressing inhibitory interneurons toward a high plasticity state. Selective deletion of the<jats:italic>Acan<\/jats:italic>gene in the visual cortex of male adult mice reinstated juvenile ocular dominance plasticity, which was mechanistically identical to critical period plasticity. Brain-wide targeting improved object recognition memory.<\/jats:p><jats:p><jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>The study provides the first direct evidence of aggrecan as the main functional constituent and orchestrator of perineuronal nets (PNNs), and that loss of PNNs by aggrecan removal induces a permanent state of critical period-like plasticity. Loss of aggrecan ablates the PNN structure, resulting in invoked juvenile plasticity in the visual cortex and enhanced object recognition memory.<\/jats:p>","DOI":"10.1523\/jneurosci.1122-18.2018","type":"journal-article","created":{"date-parts":[[2018,10,3]],"date-time":"2018-10-03T19:10:29Z","timestamp":1538593829000},"page":"10102-10113","source":"Crossref","is-referenced-by-count":225,"title":["Aggrecan Directs Extracellular Matrix-Mediated Neuronal Plasticity"],"prefix":"10.1523","volume":"38","author":[{"given":"Daire","family":"Rowlands","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3145-1659","authenticated-orcid":false,"given":"Kristian 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