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Synaptic Neurosci."],"abstract":"<jats:p>\n                    Perineuronal nets (PNNs) have an important physiological role in the retention of learning by restricting cognitive flexibility. Their deposition peaks after developmental periods of intensive learning, usually in late childhood, and they help in long-term preservation of newly acquired skills and information. Modulation of PNN function by various techniques enhances plasticity and regulates the retention of memories, which may be beneficial when memory persistence entails negative symptoms such as post-traumatic stress disorder (PTSD). In this study, we investigated the role of PTP\u03c3 [receptor-type tyrosine-protein phosphatase S, a phosphatase that is activated by binding of chondroitin sulfate proteoglycans (CSPGs) from PNNs] in retention of memories using Novel Object Recognition and Fear Conditioning models. We observed that mice haploinsufficient for\n                    <jats:italic>PTPRS<\/jats:italic>\n                    gene (PTP\u03c3\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    ), although having improved short-term object recognition memory, display impaired long-term memory in both Novel Object Recognition and Fear Conditioning paradigm, as compared to WT littermates. However, PTP\u03c3\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    mice did not show any differences in behavioral tests that do not heavily rely on cognitive flexibility, such as Elevated Plus Maze, Open Field, Marble Burying, and Forced Swimming Test. Since PTP\u03c3 has been shown to interact with and dephosphorylate TRKB, we investigated activation of this receptor and its downstream pathways in limbic areas known to be associated with memory. We found that phosphorylation of TRKB and PLC\u03b3 are increased in the hippocampus, prefrontal cortex, and amygdaloid complex of PTP\u03c3\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    mice, but other TRKB-mediated signaling pathways are not affected. Our data suggest that PTP\u03c3 downregulation promotes TRKB phosphorylation in different brain areas, improves short-term memory performance but disrupts long-term memory retention in the tested animal models. Inhibition of PTP\u03c3 or disruption of PNN-PTP\u03c3-TRKB complex might be a potential target for disorders where negative modulation of the acquired memories can be beneficial.\n                  <\/jats:p>","DOI":"10.3389\/fnsyn.2021.672475","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T14:20:09Z","timestamp":1626963609000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Perineuronal Net Receptor PTP\u03c3 Regulates Retention of Memories"],"prefix":"10.3389","volume":"13","author":[{"given":"Angelina","family":"Lesnikova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Plinio","family":"Casarotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Moliner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senem Merve","family":"Fred","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Biojone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eero","family":"Castr\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1111\/j.1601-183X.2012.00801.x","article-title":"Fear extinction and BDNF: translating animal models of PTSD to the clinic","volume":"11","author":"Andero","year":"2012","journal-title":"Genes Brain Behav."},{"key":"B2","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.jneumeth.2013.11.001","article-title":"Utilization of in situ ELISA method for examining Trk receptor phosphorylation in cultured cells","volume":"222","author":"Antila","year":"2014","journal-title":"J. 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