{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:31:02Z","timestamp":1790839862066,"version":"4.1.0"},"reference-count":76,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["MH086403"],"award-info":[{"award-number":["MH086403"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD084215"],"award-info":[{"award-number":["HD084215"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS11566001"],"award-info":[{"award-number":["NS11566001"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["1P50HD104458"],"award-info":[{"award-number":["1P50HD104458"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015521","name":"Stanford Maternal and Child Health Research Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015521","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Fragile X syndrome (FXS) is an X chromosome-linked disease associated with severe intellectual disabilities. Previous studies using the\n                    <jats:italic>Fmr1<\/jats:italic>\n                    knockout (KO) mouse, an FXS mouse model, have attributed behavioral deficits to synaptic dysfunctions. However, how functional deficits at neural network level lead to abnormal behavioral learning remains unexplored. Here, we show that the efficacy of hippocampal engram reactivation is reduced in\n                    <jats:italic>Fmr1<\/jats:italic>\n                    KO mice performing contextual fear memory recall. Experiencing an enriched environment (EE) prior to learning improved the engram reactivation efficacy and rescued memory recall in the\n                    <jats:italic>Fmr1<\/jats:italic>\n                    KO mice. In addition, chemogenetically inhibiting EE-engaged neurons in CA1 reverses the rescue effect of EE on memory recall. Thus, our results suggest that inappropriate engram reactivation underlies cognitive deficits in FXS, and enriched environment may rescue cognitive deficits by improving network activation accuracy.\n                  <\/jats:p>","DOI":"10.7554\/elife.61882","type":"journal-article","created":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T05:00:44Z","timestamp":1605848444000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.61882","source":"Crossref","is-referenced-by-count":31,"title":["Defective memory engram reactivation underlies impaired fear memory recall in Fragile X syndrome"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7009-5680","authenticated-orcid":true,"given":"Jie","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rena Y","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin L","family":"Arendt","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Tien","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia R","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8097-2699","authenticated-orcid":true,"given":"Lu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2020,11,20]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26853-z","article-title":"Impaired hippocampal representation of place in the Fmr1-knockout mouse model of fragile X syndrome","volume":"8","author":"Arbab","year":"2018","journal-title":"Scientific Reports"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1111\/j.1460-9568.2005.04552.x","article-title":"Long-lasting modulation of the induction of LTD and LTP in rat hippocampal CA1 by behavioural stress and environmental enrichment","volume":"23","author":"Artola","year":"2006","journal-title":"European Journal of Neuroscience"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1038\/nature11737","article-title":"FMRP targets distinct mRNA sequence elements to regulate protein expression","volume":"492","author":"Ascano","year":"2012","journal-title":"Nature"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"4314","DOI":"10.1172\/JCI63141","article-title":"Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics","volume":"122","author":"Bagni","year":"2012","journal-title":"Journal of Clinical Investigation"},{"key":"bib5","first-page":"23","article-title":"Fmr1 knockout mice: a model to study fragile X mental retardation. 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