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A key feature of FXS symptomatology is altered sensory processing greatly affecting FXS individual\u2019s life quality. Here, we use a combination of behavioral tests and slice physiology tools to study the neurophysiological alterations underlying aberrant sensory processing in the olfactory system of the FXS mouse model (<jats:italic>Fmr1<\/jats:italic> KO). We focused on the piriform cortex (PC), since it is in this brain region where olfactory information is integrated and ultimately decoded. Using a go-no go behavioral task we have found that <jats:italic>Fmr1<\/jats:italic> KO learn to discriminate between a rewarded and a not rewarded odorant but cannot distinguish complex odor mixtures, akin to what is found in the environment. Moreover, <jats:italic>Fmr1<\/jats:italic> KO long-term memory is impaired compared to control mice suggesting possibly cortical processing alterations. In addition, electrophysiological data from PC layer II neurons of <jats:italic>Fmr1<\/jats:italic> KO mice showed a hyperexcitable phenotype manifested by differences in active membrane properties and altered network connectivity. Taken together, our data suggest a possible causal link between the observed olfactory discrimination deficiencies in the <jats:italic>Fmr1<\/jats:italic> KO mouse and the altered physiology of PC.<\/jats:p>","DOI":"10.1186\/s40659-024-00582-2","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T13:42:21Z","timestamp":1745502141000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Olfactory dysfunction and altered cortical excitability in the mouse model of Fragile X Syndrome"],"prefix":"10.1186","volume":"58","author":[{"given":"Felipe","family":"Arancibia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1139-9502","authenticated-orcid":false,"given":"Marcelo","family":"Rojas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Becerra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo","family":"Fuenzalida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4658-2427","authenticated-orcid":false,"given":"Christian","family":"Cea-Del Rio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Mpodozis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8073-0385","authenticated-orcid":false,"given":"Magdalena","family":"Sanhueza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0239-2493","authenticated-orcid":false,"given":"Alexia","family":"Nunez-Parra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"582_CR1","doi-asserted-by":"publisher","first-page":"17065","DOI":"10.1038\/nrdp.2017.65","volume":"3","author":"RJ Hagerman","year":"2017","unstructured":"Hagerman RJ, Berry-Kravis E, Hazlett HC, Bailey DB Jr., Moine H, Kooy RF, Tassone F, Gantois I, Sonenberg N, Mandel JL, et al. 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