{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:35:31Z","timestamp":1771461331758,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,4,30]],"date-time":"2014-04-30T00:00:00Z","timestamp":1398816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000297","name":"Fraxa Research Foundation","doi-asserted-by":"crossref","award":["Autism Science Foundation"],"award-info":[{"award-number":["Autism Science Foundation"]}],"id":[{"id":"10.13039\/100000297","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000297","name":"Fraxa Research Foundation","doi-asserted-by":"crossref","award":["National Institute of Mental Health"],"award-info":[{"award-number":["National Institute of Mental Health"]}],"id":[{"id":"10.13039\/100000297","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000297","name":"Fraxa Research Foundation","doi-asserted-by":"crossref","award":["2T32MH074249"],"award-info":[{"award-number":["2T32MH074249"]}],"id":[{"id":"10.13039\/100000297","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute of Child Health and Development","award":["5RO1HD046903"],"award-info":[{"award-number":["5RO1HD046903"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Brain and Behavior"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:p><jats:bold>Fragile X (FX) is the most common genetic cause of intellectual disability and autism. Previous studies have shown that partial inhibition of metabotropic glutamate receptor signaling is sufficient to correct behavioral phenotypes in a mouse model of FX, including audiogenic seizures, open\u2010field hyperactivity and social behavior. These phenotypes model well the epilepsy (15%), hyperactivity (20%) and autism (30%) that are comorbid with FX in human patients. Identifying reliable and robust mouse phenotypes to model cognitive impairments is critical considering the 90% comorbidity of FX and intellectual disability. Recent work characterized a five\u2010choice visuospatial discrimination assay testing cognitive flexibility, in which FX model mice show impairments associated with decreases in synaptic proteins in prefrontal cortex (PFC). In this study, we sought to determine whether instrumental extinction, another process requiring PFC, is altered in FX model mice, and whether downregulation of metabotropic glutamate receptor signaling pathways is sufficient to correct both visuospatial discrimination and extinction phenotypes. We report that instrumental extinction is consistently exaggerated in FX model mice. However, neither the extinction phenotype nor the visuospatial discrimination phenotype is corrected by approaches targeting metabotropic glutamate receptor signaling. This work describes a novel behavioral extinction assay to model impaired cognition in mouse models of neurodevelopmental disorders, provides evidence that extinction is exaggerated in the FX mouse model and suggests possible limitations of metabotropic glutamate receptor\u2010based pharmacotherapy.<\/jats:bold><\/jats:p>","DOI":"10.1111\/gbb.12137","type":"journal-article","created":{"date-parts":[[2014,3,31]],"date-time":"2014-03-31T13:36:52Z","timestamp":1396273012000},"page":"451-458","source":"Crossref","is-referenced-by-count":23,"title":["Extinction of an instrumental response: a cognitive behavioral assay in <i>Fmr1<\/i> knockout mice"],"prefix":"10.1111","volume":"13","author":[{"given":"M. S.","family":"Sidorov","sequence":"first","affiliation":[{"name":"The Picower Institute for Learning and Memory Massachusetts Institute of Technology  Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. D.","family":"Krueger","sequence":"additional","affiliation":[{"name":"The Picower Institute for Learning and Memory Massachusetts Institute of Technology  Cambridge MA USA"},{"name":"Present address: Department of Molecular Neurobiology Max Planck Institute for Experimental Medicine  Goettingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Taylor","sequence":"additional","affiliation":[{"name":"The Picower Institute for Learning and Memory Massachusetts Institute of Technology  Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Gisin","sequence":"additional","affiliation":[{"name":"The Picower Institute for Learning and Memory Massachusetts Institute of Technology  Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. 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