{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:35:11Z","timestamp":1791246911697,"version":"4.1.0"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01MH126176"],"award-info":[{"award-number":["R01MH126176"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Alterations in neuronal plasticity and critical periods are common across neurodevelopmental diseases, including Fragile X syndrome (FXS), the leading single-gene cause of autism. Characterized with sensory dysfunction, FXS is the result of gene silencing of <jats:italic>Fragile X messenger ribonucleoprotein 1 (FMR1)<\/jats:italic> and loss of its product, Fragile X messenger ribonucleoprotein (FMRP). The mechanisms underlying altered critical period and sensory dysfunction in FXS are obscure. Here, we performed genetic and surgical deprivation of peripheral auditory inputs in wildtype and <jats:italic>Fmr1<\/jats:italic> knockout (KO) mice across ages and investigated the effects of global FMRP loss on deafferentation-induced neuronal changes in the ventral cochlear nucleus (VCN) and auditory brainstem responses. The degree of neuronal cell loss during the critical period was unchanged in <jats:italic>Fmr1<\/jats:italic> KO mice. However, the closure of the critical period was delayed. Importantly, this delay was temporally coincidental with reduced hearing sensitivity, implying an association with sensory inputs. Functional analyses further identified early-onset and long-lasting alterations in signal transmission from the spiral ganglion to the VCN, suggesting a peripheral site of FMRP action. Finally, we generated conditional <jats:italic>Fmr1<\/jats:italic> KO (cKO) mice with selective deletion of FMRP in spiral ganglion but not VCN neurons. cKO mice recapitulated the delay in the VCN critical period closure in <jats:italic>Fmr1<\/jats:italic> KO mice, confirming an involvement of cochlear FMRP in shaping the temporal features of neuronal critical periods in the brain. Together, these results identify a novel peripheral mechanism of neurodevelopmental pathogenesis.<\/jats:p>","DOI":"10.3389\/fncel.2023.1186630","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T04:37:50Z","timestamp":1684989470000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Peripheral Fragile X messenger ribonucleoprotein is required for the timely closure of a critical period for neuronal susceptibility in the ventral cochlear nucleus"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaoyan","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.1768","article-title":"Mouse auditory brainstem response testing.","volume":"6","author":"Akil","year":"2016","journal-title":"Bio Protoc."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30455-9","article-title":"Auditory processing remains sensitive to environmental experience during adolescence in a rodent model.","volume":"13","author":"Anbuhl","year":"2022","journal-title":"Nat. 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