{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:01:48Z","timestamp":1790805708107,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondation pour l\u2019audition","award":["FPA-RD-2020-8"],"award-info":[{"award-number":["FPA-RD-2020-8"]}]},{"name":"Fondation pour l\u2019audition","award":["FPA IDA09"],"award-info":[{"award-number":["FPA IDA09"]}]},{"name":"Association Autour de Williams","award":["FPA-RD-2020-8"],"award-info":[{"award-number":["FPA-RD-2020-8"]}]},{"name":"Association Autour de Williams","award":["FPA IDA09"],"award-info":[{"award-number":["FPA IDA09"]}]},{"name":"Williams France","award":["FPA-RD-2020-8"],"award-info":[{"award-number":["FPA-RD-2020-8"]}]},{"name":"Williams France","award":["FPA IDA09"],"award-info":[{"award-number":["FPA IDA09"]}]},{"name":"CNRS and Bordeaux University","award":["FPA-RD-2020-8"],"award-info":[{"award-number":["FPA-RD-2020-8"]}]},{"name":"CNRS and Bordeaux University","award":["FPA IDA09"],"award-info":[{"award-number":["FPA IDA09"]}]},{"name":"Fondation pour l\u2019audition","award":["FPA-RD-2020-8"],"award-info":[{"award-number":["FPA-RD-2020-8"]}]},{"name":"Fondation pour l\u2019audition","award":["FPA IDA09"],"award-info":[{"award-number":["FPA IDA09"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hyperacusis, i.e., an increased sensitivity to sounds, is described in several neurodevelopmental disorders (NDDs), including Fragile X Syndrome (FXS). The mechanisms underlying hyperacusis in FXS are still largely unknown and effective therapies are lacking. Big conductance calcium-activated potassium (BKCa) channels were proposed as a therapeutic target to treat several behavioral disturbances in FXS preclinical models, but their role in mediating their auditory alterations was not specifically addressed. Furthermore, studies on the acoustic phenotypes of FXS animal models mostly focused on central rather than peripheral auditory pathways. Here, we provided an extensive characterization of the peripheral auditory phenotype of the Fmr1-knockout (KO) mouse model of FXS at adulthood. We also assessed whether the acute administration of Chlorzoxazone, a BKCa agonist, could rescue the auditory abnormalities of adult mutant mice. Fmr1-KO mice both at 3 and 6 months showed a hyperacusis-like startle phenotype with paradoxically reduced auditory brainstem responses associated with a loss of ribbon synapses in the inner hair cells (IHCs) compared to their wild-type (WT) littermates. BKCa expression was markedly reduced in the IHCs of KOs compared to WT mice, but only at 6 months, when Chlorzoxazone rescued mutant auditory dysfunction. Our findings highlight the age-dependent and progressive contribution of peripheral mechanisms and BKCa channels to adult hyperacusis in FXS, suggesting a novel therapeutic target to treat auditory dysfunction in NDDs.<\/jats:p>","DOI":"10.3390\/ijms241411863","type":"journal-article","created":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T01:21:27Z","timestamp":1690248087000},"page":"11863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Hyperacusis in the Adult Fmr1-KO Mouse Model of Fragile X Syndrome: The Therapeutic Relevance of Cochlear Alterations and BKCa Channels"],"prefix":"10.3390","volume":"24","author":[{"given":"Celeste","family":"Ferraguto","sequence":"first","affiliation":[{"name":"Univ. Bordeaux, CNRS, EPHE, INCIA, UMR 5287, F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohan","family":"Bouleau","sequence":"additional","affiliation":[{"name":"Neurophysiologie de la Synapse Auditive, Universit\u00e9 de Bordeaux, INSERM UA06, F-33000 Bordeaux, France"},{"name":"Institut de l\u2019Audition, Centre Institut Pasteur, Inserm UA06, F-75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1039-099X","authenticated-orcid":false,"given":"Thibault","family":"Peineau","sequence":"additional","affiliation":[{"name":"Neurophysiologie de la Synapse Auditive, Universit\u00e9 de Bordeaux, INSERM UA06, F-33000 Bordeaux, France"},{"name":"Institut de l\u2019Audition, Centre Institut Pasteur, Inserm UA06, F-75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1541-6861","authenticated-orcid":false,"given":"Didier","family":"Dulon","sequence":"additional","affiliation":[{"name":"Neurophysiologie de la Synapse Auditive, Universit\u00e9 de Bordeaux, INSERM UA06, F-33000 Bordeaux, France"},{"name":"Institut de l\u2019Audition, Centre Institut Pasteur, Inserm UA06, F-75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8993-1922","authenticated-orcid":false,"given":"Susanna","family":"Pietropaolo","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux, CNRS, EPHE, INCIA, UMR 5287, F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17065","DOI":"10.1038\/nrdp.2017.65","article-title":"Fragile X syndrome","volume":"3","author":"Hagerman","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7101","DOI":"10.1073\/pnas.141145998","article-title":"Synaptic regulation of protein synthesis and the fragile X protein","volume":"98","author":"Greenough","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1352\/1944-7558-115.6.461","article-title":"Seizures in fragile X syndrome: Characteristics and comorbid diagnoses","volume":"115","author":"Raspa","year":"2010","journal-title":"Am. J. Intellect. Dev. Disabil."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s11689-010-9067-y","article-title":"Clinical assessment of DSM-IV anxiety disorders in fragile X syndrome: Prevalence and characterization","volume":"3","author":"Cordeiro","year":"2011","journal-title":"J. Neurodev. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1007\/s10803-017-3081-9","article-title":"Autism Spectrum Disorder Symptoms in Infants with Fragile X Syndrome: A Prospective Case Series","volume":"47","author":"Hogan","year":"2017","journal-title":"J. Autism Dev. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/(SICI)1096-8628(19990402)83:4<268::AID-AJMG7>3.0.CO;2-K","article-title":"Electrodermal responses to sensory stimuli in individuals with fragile X syndrome: A preliminary report","volume":"83","author":"Miller","year":"1999","journal-title":"Am. J. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fncel.2014.00019","article-title":"Auditory processing in fragile X syndrome","volume":"8","author":"Rotschafer","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"90","DOI":"10.2310\/7070.2001.20811","article-title":"Hyperacusis in Williams syndrome","volume":"30","author":"Johnson","year":"2001","journal-title":"J. Otolaryngol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ralli, M., Romani, M., Zodda, A., Russo, F.Y., Altissimi, G., Orlando, M.P., Cammeresi, M.G., Penge, R., and Turchetta, R. (2020). Hyperacusis in Children with Attention Deficit Hyperactivity Disorder: A Preliminary Study. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17093045"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1007\/s00405-013-2482-4","article-title":"Auditory profile and high resolution CT scan in autism spectrum disorders children with auditory hypersensitivity","volume":"270","author":"Thabet","year":"2013","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/bs.irn.2016.03.016","article-title":"BK Channels in the Vertebrate Inner Ear","volume":"128","author":"Pyott","year":"2016","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1152\/jn.01155.2002","article-title":"Contribution of BK Ca2+-activated K+ channels to auditory neurotransmission in the Guinea pig cochlea","volume":"90","author":"Skinner","year":"2003","journal-title":"J. Neurophysiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"756449","DOI":"10.3389\/fnagi.2021.756449","article-title":"Synaptic Release Potentiation at Aging Auditory Ribbon Synapses","volume":"13","author":"Peineau","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/nature03418","article-title":"Hair cell synaptic ribbons are essential for synchronous auditory signalling","volume":"434","author":"Khimich","year":"2005","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s00441-014-2102-7","article-title":"Relating structure and function of inner hair cell ribbon synapses","volume":"361","author":"Wichmann","year":"2015","journal-title":"Cell Tissue Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0301-0082(02)00004-7","article-title":"Channels underlying neuronal calcium-activated potassium currents","volume":"66","author":"Sah","year":"2002","journal-title":"Prog. Neurobiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s13023-014-0124-6","article-title":"Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by a BKCa channel opener molecule","volume":"9","author":"Pietropaolo","year":"2014","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1176\/ajp.2006.163.9.1622","article-title":"Association of a functional deficit of the BKCa channel, a synaptic regulator of neuronal excitability, with autism and mental retardation","volume":"163","author":"Laumonnier","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1093\/hmg\/ddz117","article-title":"De novo loss-of-function KCNMA1 variants are associated with a new multiple malformation syndrome and a broad spectrum of developmental and neurological phenotypes","volume":"28","author":"Liang","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13041-015-0168-0","article-title":"Human induced pluripotent stem cell derived neurons as a model for Williams-Beuren syndrome","volume":"8","author":"Khattak","year":"2015","journal-title":"Mol. Brain"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lemaire-Mayo, V., Piquemal, M., Crusio, W.E., Louette, E., and Pietropaolo, S. (2020). Therapeutic effects of Chlorzoxazone, a BKCa channel agonist, in a mouse model of Fragile X syndrome. bioRxiv, preprint.","DOI":"10.1101\/2020.12.11.389569"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1038\/nn.3864","article-title":"Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1\u2212\/y mice","volume":"17","author":"Zhang","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Consorthium, The Dutch-Belgian Fragile X, Bakker, C.E., Verheij, C., Willemsen, R., van der Helm, R., Oerlemans, F., Vermey, M., Bygrave, A., Hoogeveen, A., and Oostra, B.A. (1994). Fmr1 knockout mice: A model to study fragile X mental retardation. Cell, 78, 23\u201333.","DOI":"10.1016\/0092-8674(94)90569-X"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"104722","DOI":"10.1016\/j.neubiorev.2022.104722","article-title":"Translational validity and methodological underreporting in animal research: A systematic review and meta-analysis of the Fragile X syndrome (Fmr1 KO) rodent model","volume":"139","author":"Kat","year":"2022","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1002\/aur.1814","article-title":"Behavioral abnormalities in the Fmr1-KO2 mouse model of fragile X syndrome: The relevance of early life phases","volume":"10","author":"Gaudissard","year":"2017","journal-title":"Autism Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1002\/aur.1743","article-title":"Age-specific autistic-like behaviors in heterozygous Fmr1-KO female mice","volume":"10","author":"Gauducheau","year":"2017","journal-title":"Autism Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.bbr.2014.05.046","article-title":"Behavioral analysis of male and female Fmr1 knockout mice on C57BL\/6 background","volume":"271","author":"Ding","year":"2014","journal-title":"Behav. Brain Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/sj.mp.4001432","article-title":"Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice","volume":"9","author":"Frankland","year":"2004","journal-title":"Mol. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1159\/000332884","article-title":"The GABA(A) receptor agonist THIP ameliorates specific behavioral deficits in the mouse model of fragile X syndrome","volume":"33","author":"Corbin","year":"2011","journal-title":"Dev. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.neuron.2012.03.009","article-title":"Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice","volume":"74","author":"Michalon","year":"2012","journal-title":"Neuron"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/S0006-8993(01)03309-1","article-title":"Alterations in the auditory startle response in Fmr1 targeted mutant mouse models of fragile X syndrome","volume":"927","author":"Nielsen","year":"2002","journal-title":"Brain Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4797","DOI":"10.1523\/JNEUROSCI.0839-18.2019","article-title":"Modulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice","volume":"39","author":"Song","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Rotschafer, S.E., Marshak, S., and Cramer, K.S. (2015). Deletion of Fmr1 alters function and synaptic inputs in the auditory brainstem. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0117266"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Pietropaolo, S., Guilleminot, A., Martin, B., D\u2019Amato, F.R., and Crusio, W.E. (2011). Genetic-background modulation of core and variable autistic-like symptoms in Fmr1 knock-out mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017073"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/aur.168","article-title":"Modifying behavioral phenotypes in Fmr1KO mice: Genetic background differences reveal autistic-like responses","volume":"4","author":"Spencer","year":"2011","journal-title":"Autism Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0378-5955(97)00155-X","article-title":"A major gene affecting age-related hearing loss in C57BL\/6J mice","volume":"114","author":"Johnson","year":"1997","journal-title":"Hear. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/ng1226","article-title":"Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss","volume":"35","author":"Zheng","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/S0306-4522(01)00036-7","article-title":"Fragile X mice develop sensory hyperreactivity to auditory stimuli","volume":"103","author":"Chen","year":"2001","journal-title":"Neuroscience"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7403","DOI":"10.1523\/JNEUROSCI.2310-16.2017","article-title":"Enhanced Excitatory Connectivity and Disturbed Sound Processing in the Auditory Brainstem of Fragile X Mice","volume":"37","author":"Gessele","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"15686","DOI":"10.1523\/JNEUROSCI.3246-12.2013","article-title":"Impaired critical period plasticity in primary auditory cortex of fragile X model mice","volume":"33","author":"Kim","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"720752","DOI":"10.3389\/fpsyt.2021.720752","article-title":"Neural Correlates of Auditory Hypersensitivity in Fragile X Syndrome","volume":"12","author":"Razak","year":"2021","journal-title":"Front. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.brainres.2013.02.038","article-title":"Altered auditory processing in a mouse model of fragile X syndrome","volume":"1506","author":"Rotschafer","year":"2013","journal-title":"Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"ENEURO.0264-17.2017","DOI":"10.1523\/ENEURO.0264-17.2017","article-title":"Developmental Emergence of Phenotypes in the Auditory Brainstem Nuclei of Fmr1 Knockout Mice","volume":"4","author":"Rotschafer","year":"2017","journal-title":"eNeuro"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.tins.2010.06.004","article-title":"BK channel activation: Structural and functional insights","volume":"33","author":"Lee","year":"2010","journal-title":"Trends Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0896-6273(00)00159-8","article-title":"RIBEYE, a component of synaptic ribbons: A protein\u2019s journey through evolution provides insight into synaptic ribbon function","volume":"28","author":"Schmitz","year":"2000","journal-title":"Neuron"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.1528-1157.2000.tb01499.x","article-title":"Audiogenic seizures susceptibility in transgenic mice with fragile X syndrome","volume":"41","author":"Musumeci","year":"2000","journal-title":"Epilepsia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"917183","DOI":"10.3389\/fncel.2022.917183","article-title":"Long-term behavioral effects of prenatal stress in the Fmr1-knock-out mouse model for fragile X syndrome","volume":"16","author":"Petroni","year":"2022","journal-title":"Front. Cell. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"13686","DOI":"10.1523\/JNEUROSCI.1783-13.2013","article-title":"Age-related cochlear synaptopathy: An early-onset contributor to auditory functional decline","volume":"33","author":"Sergeyenko","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1113\/JP271031","article-title":"Genetic upregulation of BK channel activity normalizes multiple synaptic and circuit defects in a mouse model of fragile X syndrome","volume":"594","author":"Deng","year":"2016","journal-title":"J. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.neuron.2012.12.018","article-title":"FMRP regulates neurotransmitter release and synaptic information transmission by modulating action potential duration via BK channels","volume":"77","author":"Deng","year":"2013","journal-title":"Neuron"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e201912502","DOI":"10.1085\/jgp.201912502","article-title":"Differential regulation of BK channels by fragile X mental retardation protein","volume":"152","author":"Kshatri","year":"2020","journal-title":"J. Gen. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8669","DOI":"10.1074\/jbc.M211661200","article-title":"Leucine zipper domain targets cAMP-dependent protein kinase to mammalian BK channels","volume":"278","author":"Tian","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1152\/jn.00058.2011","article-title":"Bidirectional control of BK channel open probability by CAMKII and PKC in medial vestibular nucleus neurons","volume":"105","year":"2011","journal-title":"J. Neurophysiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s12035-008-8039-7","article-title":"Regulation of synaptic transmission by presynaptic CaMKII and BK channels","volume":"38","author":"Wang","year":"2008","journal-title":"Mol. Neurobiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.cell.2011.06.013","article-title":"FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism","volume":"146","author":"Darnell","year":"2011","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.heares.2011.03.004","article-title":"Potassium channel modulation and auditory processing","volume":"279","author":"Brown","year":"2011","journal-title":"Hear. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"R767","DOI":"10.1016\/j.cub.2003.09.018","article-title":"Auditory physiology: Listening with K+ channels","volume":"13","author":"Eatock","year":"2003","journal-title":"Curr. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.neuropharm.2010.05.002","article-title":"Early developmental alterations in GABAergic protein expression in fragile X knockout mice","volume":"59","author":"Adusei","year":"2010","journal-title":"Neuropharmacology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6181","DOI":"10.1523\/JNEUROSCI.1047-06.2006","article-title":"The role of BKCa channels in electrical signal encoding in the mammalian auditory periphery","volume":"26","author":"Oliver","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/npp.2014.291","article-title":"Early social enrichment rescues adult behavioral and brain abnormalities in a mouse model of fragile X syndrome","volume":"40","author":"Oddi","year":"2015","journal-title":"Neuropsychopharmacology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11863\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:18:08Z","timestamp":1760127488000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,24]]},"references-count":60,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241411863"],"URL":"https:\/\/doi.org\/10.3390\/ijms241411863","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,24]]}}}