{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T03:00:03Z","timestamp":1789095603608,"version":"build-2803163510"},"reference-count":81,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000025","name":"U.S. Department of Health & Human Services | NIH | National Institute of Mental Health","doi-asserted-by":"publisher","award":["R44MH112474"],"award-info":[{"award-number":["R44MH112474"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-024-07120-6","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T17:03:38Z","timestamp":1730912618000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Deep functional measurements of Fragile X syndrome human neurons reveal multiparametric electrophysiological disease phenotype"],"prefix":"10.1038","volume":"7","author":[{"given":"James J.","family":"Fink","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2187-6867","authenticated-orcid":false,"given":"Nathaniel","family":"Delaney-Busch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Dawes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evanthia","family":"Nanou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Folts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthiayani","family":"Harikrishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Hempel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hansini","family":"Upadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trinh","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himali","family":"Shroff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Stoppel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Jacques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Grooms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7099-1522","authenticated-orcid":false,"given":"Elizabeth","family":"Berry-Kravis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9903-2541","authenticated-orcid":false,"given":"Mark F.","family":"Bear","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis A.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gerber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Bunnage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brinley","family":"Furey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9273-7506","authenticated-orcid":false,"given":"Graham T.","family":"Dempsey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,6]]},"reference":[{"key":"7120_CR1","doi-asserted-by":"publisher","unstructured":"Lozano, R., Rosero, C. A. & Hagerman, R. J. Fragile X spectrum disorders. Intractable & Rare Diseases Research, https:\/\/doi.org\/10.5582\/irdr.2014.01022 (2014).","DOI":"10.5582\/irdr.2014.01022"},{"key":"7120_CR2","doi-asserted-by":"publisher","unstructured":"Penagarikano, O., Mulle, J. G. & Warren, S. T. The Pathophysiology of Fragile X Syndrome. Annual Review of Genomics and Human Genetics, https:\/\/doi.org\/10.1146\/annurev.genom.8.080706.092249 (2007).","DOI":"10.1146\/annurev.genom.8.080706.092249"},{"key":"7120_CR3","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.65","volume":"3","author":"RJ Hagerman","year":"2017","unstructured":"Hagerman, R. J. et al. Fragile X syndrome. Nat. Rev. Dis. Prim. 3, 17065 (2017).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"7120_CR4","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/0092-8674(91)90397-H","volume":"65","author":"AJ Verkerk","year":"1991","unstructured":"Verkerk, A. J. et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65, 905\u2013914 (1991).","journal-title":"Cell"},{"key":"7120_CR5","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.cell.2011.06.013","volume":"146","author":"JC Darnell","year":"2011","unstructured":"Darnell, J. C. et al. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 146, 247\u2013261 (2011).","journal-title":"Cell"},{"key":"7120_CR6","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1146\/annurev-neuro-060909-153138","volume":"35","author":"AL Bhakar","year":"2012","unstructured":"Bhakar, A. L., D\u00f6len, G. & Bear, M. F. The pathophysiology of fragile X (and what it teaches us about synapses). Annu Rev. Neurosci. 35, 417\u2013443 (2012).","journal-title":"Annu Rev. Neurosci."},{"key":"7120_CR7","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1016\/j.cell.2017.07.033","volume":"170","author":"E Korb","year":"2017","unstructured":"Korb, E. et al. Excess Translation of Epigenetic Regulators Contributes to Fragile X Syndrome and Is Alleviated by Brd4 Inhibition. Cell 170, 1209\u20131223.e20 (2017).","journal-title":"Cell"},{"key":"7120_CR8","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1038\/nrn4001","volume":"16","author":"JD Richter","year":"2015","unstructured":"Richter, J. D., Bassell, G. J. & Klann, E. Dysregulation and restoration of translational homeostasis in fragile X syndrome. Nat. Rev. Neurosci. 16, 595\u2013605 (2015).","journal-title":"Nat. Rev. Neurosci."},{"key":"7120_CR9","doi-asserted-by":"crossref","unstructured":"Hale, C. R. et al. FMRP regulates mRNAs encoding distinct functions in the cell body and dendrites of CA1 pyramidal neurons. Elife 10, e71892 (2021).","DOI":"10.7554\/eLife.71892"},{"key":"7120_CR10","doi-asserted-by":"publisher","first-page":"7101","DOI":"10.1073\/pnas.141145998","volume":"98","author":"WT Greenough","year":"2001","unstructured":"Greenough, W. T. et al. Synaptic regulation of protein synthesis and the fragile X protein. Proc. Natl Acad. Sci. USA 98, 7101\u20137106 (2001).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"7120_CR11","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/S0092-8674(03)00079-5","volume":"112","author":"F Zalfa","year":"2003","unstructured":"Zalfa, F. et al. The fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at synapses. Cell 112, 317\u2013327 (2003).","journal-title":"Cell"},{"key":"7120_CR12","doi-asserted-by":"publisher","unstructured":"Bear, M. F., Huber, K. M. & Warren, S. T. The mGluR theory of fragile X mental retardation. Trends Neurosci. https:\/\/doi.org\/10.1016\/j.tins.2004.04.009 (2004).","DOI":"10.1016\/j.tins.2004.04.009"},{"key":"7120_CR13","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/j.neuron.2007.12.001","volume":"56","author":"G D\u00f6len","year":"2007","unstructured":"D\u00f6len, G. et al. Correction of fragile X syndrome in mice. Neuron 56, 955\u2013962 (2007).","journal-title":"Neuron"},{"key":"7120_CR14","doi-asserted-by":"publisher","first-page":"15616","DOI":"10.1523\/JNEUROSCI.3888-10.2010","volume":"30","author":"EK Osterweil","year":"2010","unstructured":"Osterweil, E. K., Krueger, D. D., Reinhold, K. & Bear, M. F. Hypersensitivity to mGluR5 and ERK1\/2 leads to excessive protein synthesis in the hippocampus of a mouse model of fragile X syndrome. J. Neurosci. 30, 15616\u201315627 (2010).","journal-title":"J. Neurosci."},{"key":"7120_CR15","doi-asserted-by":"publisher","first-page":"5087","DOI":"10.1523\/JNEUROSCI.0093-05.2005","volume":"25","author":"M Qin","year":"2005","unstructured":"Qin, M., Kang, J., Burlin, T. V., Jiang, C. & Smith, C. B. Postadolescent changes in regional cerebral protein synthesis: an in vivo study in the FMR1 null mouse. J. Neurosci. 25, 5087\u20135095 (2005).","journal-title":"J. Neurosci."},{"key":"7120_CR16","doi-asserted-by":"crossref","unstructured":"Fmr1 knockout mice: a model to study fragile X mental retardation. The Dutch-Belgian Fragile X Consortium. Cell 78, 23\u201333 (1994).","DOI":"10.1016\/0092-8674(94)90569-X"},{"key":"7120_CR17","doi-asserted-by":"publisher","first-page":"51","DOI":"10.3389\/fnmol.2019.00051","volume":"12","author":"M Telias","year":"2019","unstructured":"Telias, M. Molecular Mechanisms of Synaptic Dysregulation in Fragile X Syndrome and Autism Spectrum Disorders. Front Mol. Neurosci. 12, 51 (2019).","journal-title":"Front Mol. Neurosci."},{"key":"7120_CR18","doi-asserted-by":"publisher","unstructured":"Contractor, A., Klyachko, V. A. & Portera-Cailliau, C. Altered Neuronal and Circuit Excitability in Fragile X Syndrome. Neuron https:\/\/doi.org\/10.1016\/j.neuron.2015.06.017 (2015).","DOI":"10.1016\/j.neuron.2015.06.017"},{"key":"7120_CR19","doi-asserted-by":"publisher","first-page":"7746","DOI":"10.1073\/pnas.122205699","volume":"99","author":"KM Huber","year":"2002","unstructured":"Huber, K. M., Gallagher, S. M., Warren, S. T. & Bear, M. F. Altered synaptic plasticity in a mouse model of fragile X mental retardation. PNAS 99, 7746\u20137750 (2002).","journal-title":"PNAS"},{"key":"7120_CR20","doi-asserted-by":"publisher","first-page":"5178","DOI":"10.1523\/JNEUROSCI.1076-08.2008","volume":"28","author":"I Bureau","year":"2008","unstructured":"Bureau, I., Shepherd, G. M. G. & Svoboda, K. Circuit and plasticity defects in the developing somatosensory cortex of FMR1 knock-out mice. J. Neurosci. 28, 5178\u20135188 (2008).","journal-title":"J. Neurosci."},{"key":"7120_CR21","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1006\/mcne.2001.1085","volume":"19","author":"J Li","year":"2002","unstructured":"Li, J., Pelletier, M. R., Perez Velazquez, J.-L. & Carlen, P. L. Reduced cortical synaptic plasticity and GluR1 expression associated with fragile X mental retardation protein deficiency. Mol. Cell Neurosci. 19, 138\u2013151 (2002).","journal-title":"Mol. Cell Neurosci."},{"key":"7120_CR22","doi-asserted-by":"publisher","first-page":"2264","DOI":"10.1152\/jn.00421.2011","volume":"106","author":"SM Paluszkiewicz","year":"2011","unstructured":"Paluszkiewicz, S. M., Olmos-Serrano, J. L., Corbin, J. G. & Huntsman, M. M. Impaired inhibitory control of cortical synchronization in fragile X syndrome. J. Neurophysiol. 106, 2264\u20132272 (2011).","journal-title":"J. Neurophysiol."},{"key":"7120_CR23","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1152\/jn.00221.2006","volume":"96","author":"NS Desai","year":"2006","unstructured":"Desai, N. S., Casimiro, T. M., Gruber, S. M. & Vanderklish, P. W. Early postnatal plasticity in neocortex of Fmr1 knockout mice. J. Neurophysiol. 96, 1734\u20131745 (2006).","journal-title":"J. Neurophysiol."},{"key":"7120_CR24","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.neuron.2010.01.024","volume":"65","author":"EG Harlow","year":"2010","unstructured":"Harlow, E. G. et al. Critical period plasticity is disrupted in the barrel cortex of FMR1 knockout mice. Neuron 65, 385\u2013398 (2010).","journal-title":"Neuron"},{"key":"7120_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12736-y","volume":"10","author":"APF Domanski","year":"2019","unstructured":"Domanski, A. P. F., Booker, S. A., Wyllie, D. J. A., Isaac, J. T. R. & Kind, P. C. Cellular and synaptic phenotypes lead to disrupted information processing in Fmr1-KO mouse layer 4 barrel cortex. Nat. Commun. 10, 4814 (2019).","journal-title":"Nat. Commun."},{"key":"7120_CR26","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1093\/cercor\/bht237","volume":"25","author":"CA Bostrom","year":"2015","unstructured":"Bostrom, C. A. et al. Rescue of NMDAR-dependent synaptic plasticity in Fmr1 knock-out mice. Cereb. Cortex 25, 271\u2013279 (2015).","journal-title":"Cereb. Cortex"},{"key":"7120_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.104959","volume":"142","author":"CA Cea-Del Rio","year":"2020","unstructured":"Cea-Del Rio, C. A. et al. Disrupted inhibitory plasticity and homeostasis in Fragile X syndrome. Neurobiol. Dis. 142, 104959 (2020).","journal-title":"Neurobiol. Dis."},{"key":"7120_CR28","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1093\/cercor\/10.10.1038","volume":"10","author":"SA Irwin","year":"2000","unstructured":"Irwin, S. A., Galvez, R. & Greenough, W. T. Dendritic spine structural anomalies in fragile-X mental retardation syndrome. Cereb. Cortex 10, 1038\u20131044 (2000).","journal-title":"Cereb. Cortex"},{"key":"7120_CR29","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1002\/1096-8628(20010115)98:2<161::AID-AJMG1025>3.0.CO;2-B","volume":"98","author":"SA Irwin","year":"2001","unstructured":"Irwin, S. A. et al. Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am. J. Med. Genet. 98, 161\u2013167 (2001).","journal-title":"Am. J. Med. Genet."},{"key":"7120_CR30","doi-asserted-by":"publisher","first-page":"5139","DOI":"10.1523\/JNEUROSCI.21-14-05139.2001","volume":"21","author":"EA Nimchinsky","year":"2001","unstructured":"Nimchinsky, E. A., Oberlander, A. M. & Svoboda, K. Abnormal development of dendritic spines in FMR1 knock-out mice. J. Neurosci. 21, 5139\u20135146 (2001).","journal-title":"J. Neurosci."},{"key":"7120_CR31","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.neuroscience.2012.03.049","volume":"251","author":"CX He","year":"2013","unstructured":"He, C. X. & Portera-Cailliau, C. The trouble with spines in fragile X syndrome: density, maturity and plasticity. Neuroscience 251, 120\u2013128 (2013).","journal-title":"Neuroscience"},{"key":"7120_CR32","doi-asserted-by":"publisher","first-page":"2615","DOI":"10.1152\/jn.90752.2008","volume":"100","author":"JR Gibson","year":"2008","unstructured":"Gibson, J. R., Bartley, A. F., Hays, S. A. & Huber, K. M. Imbalance of neocortical excitation and inhibition and altered UP states reflect network hyperexcitability in the mouse model of fragile X syndrome. J. Neurophysiol. 100, 2615\u20132626 (2008).","journal-title":"J. Neurophysiol."},{"key":"7120_CR33","doi-asserted-by":"crossref","unstructured":"B\u00fclow, P., Segal, M. & Bassell, G. J. Mechanisms Driving the Emergence of Neuronal Hyperexcitability in Fragile X Syndrome. Int. J. Mol. Sci. 23, 6315 (2022).","DOI":"10.3390\/ijms23116315"},{"key":"7120_CR34","doi-asserted-by":"publisher","first-page":"805929","DOI":"10.3389\/fnmol.2021.805929","volume":"14","author":"X Liu","year":"2021","unstructured":"Liu, X., Kumar, V., Tsai, N.-P. & Auerbach, B. D. Hyperexcitability and Homeostasis in Fragile X Syndrome. Front. Mol. Neurosci. 14, 805929 (2021).","journal-title":"Front. Mol. Neurosci."},{"key":"7120_CR35","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1111\/j.1469-8749.2002.tb00277.x","volume":"44","author":"E Berry-Kravis","year":"2002","unstructured":"Berry-Kravis, E. Epilepsy in fragile X syndrome. Dev. Med. Child Neurol. 44, 724\u2013728 (2002).","journal-title":"Dev. Med. Child Neurol."},{"key":"7120_CR36","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1352\/1944-7558-115.6.461","volume":"115","author":"E Berry-Kravis","year":"2010","unstructured":"Berry-Kravis, E. et al. Seizures in fragile X syndrome: characteristics and comorbid diagnoses. Am. J. Intellect. Dev. Disabil. 115, 461\u2013472 (2010).","journal-title":"Am. J. Intellect. Dev. Disabil."},{"key":"7120_CR37","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1111\/j.1528-1157.2000.tb01499.x","volume":"41","author":"SA Musumeci","year":"2000","unstructured":"Musumeci, S. A. et al. Audiogenic seizures susceptibility in transgenic mice with fragile X syndrome. Epilepsia 41, 19\u201323 (2000).","journal-title":"Epilepsia"},{"key":"7120_CR38","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/S0306-4522(01)00036-7","volume":"103","author":"L Chen","year":"2001","unstructured":"Chen, L. & Toth, M. Fragile X mice develop sensory hyperreactivity to auditory stimuli. Neuroscience 103, 1043\u20131050 (2001).","journal-title":"Neuroscience"},{"key":"7120_CR39","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s11689-017-9191-z","volume":"9","author":"J Wang","year":"2017","unstructured":"Wang, J. et al. A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome. J. Neurodev. Disord. 9, 11 (2017).","journal-title":"J. Neurodev. Disord."},{"key":"7120_CR40","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3389\/fnint.2019.00060","volume":"13","author":"LE Ethridge","year":"2019","unstructured":"Ethridge, L. E. et al. Auditory EEG Biomarkers in Fragile X Syndrome: Clinical Relevance. Front Integr. Neurosci. 13, 60 (2019).","journal-title":"Front Integr. Neurosci."},{"key":"7120_CR41","doi-asserted-by":"publisher","first-page":"720752","DOI":"10.3389\/fpsyt.2021.720752","volume":"12","author":"KA Razak","year":"2021","unstructured":"Razak, K. A., Binder, D. K. & Ethell, I. M. Neural Correlates of Auditory Hypersensitivity in Fragile X Syndrome. Front. Psychiatry 12, 720752 (2021).","journal-title":"Front. Psychiatry"},{"key":"7120_CR42","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/s41583-021-00445-9","volume":"22","author":"P-Y Deng","year":"2021","unstructured":"Deng, P.-Y. & Klyachko, V. A. Channelopathies in fragile X syndrome. Nat. Rev. Neurosci. 22, 275\u2013289 (2021).","journal-title":"Nat. Rev. Neurosci."},{"key":"7120_CR43","doi-asserted-by":"crossref","unstructured":"Vadodaria, K. C., Jones, J. R., Linker, S. & Gage, F. H. Modeling Brain Disorders Using Induced Pluripotent Stem Cells. Cold Spring Harb. Perspect. Biol. 12, a035659 (2020).","DOI":"10.1101\/cshperspect.a035659"},{"key":"7120_CR44","doi-asserted-by":"publisher","first-page":"78","DOI":"10.3389\/fnmol.2016.00078","volume":"9","author":"S Barral","year":"2016","unstructured":"Barral, S. & Kurian, M. A. Utility of Induced Pluripotent Stem Cells for the Study and Treatment of Genetic Diseases: Focus on Childhood Neurological Disorders. Front Mol. Neurosci. 9, 78 (2016).","journal-title":"Front Mol. Neurosci."},{"key":"7120_CR45","doi-asserted-by":"crossref","unstructured":"Abu Diab, M. & Eiges, R. The Contribution of Pluripotent Stem Cell (PSC)-Based Models to the Study of Fragile X Syndrome (FXS). Brain Sci. 9, 42 (2019).","DOI":"10.3390\/brainsci9020042"},{"key":"7120_CR46","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1016\/j.stemcr.2016.10.004","volume":"7","author":"U Brykczynska","year":"2016","unstructured":"Brykczynska, U. et al. CGG Repeat-Induced FMR1 Silencing Depends on the Expansion Size in Human iPSCs and Neurons Carrying Unmethylated Full Mutations. Stem Cell Rep. 7, 1059\u20131071 (2016).","journal-title":"Stem Cell Rep."},{"key":"7120_CR47","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-016-0105-9","volume":"7","author":"Y Zhou","year":"2016","unstructured":"Zhou, Y., Kumari, D., Sciascia, N. & Usdin, K. CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons. Mol. Autism 7, 42 (2016).","journal-title":"Mol. Autism"},{"key":"7120_CR48","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1016\/j.celrep.2019.02.026","volume":"26","author":"D Vershkov","year":"2019","unstructured":"Vershkov, D. et al. FMR1 Reactivating Treatments in Fragile X iPSC-Derived Neural Progenitors In Vitro and In Vivo. Cell Rep. 26, 2531\u20132539.e4 (2019).","journal-title":"Cell Rep."},{"key":"7120_CR49","doi-asserted-by":"publisher","unstructured":"Sheridan, S. D. et al. Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome. PLoS ONE https:\/\/doi.org\/10.1371\/journal.pone.0026203 (2011).","DOI":"10.1371\/journal.pone.0026203"},{"key":"7120_CR50","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1089\/scd.2014.0030","volume":"23","author":"ME Doers","year":"2014","unstructured":"Doers, M. E. et al. iPSC-Derived Forebrain Neurons from FXS Individuals Show Defects in Initial Neurite Outgrowth. Stem Cells Dev. 23, 1777\u20131787 (2014).","journal-title":"Stem Cells Dev."},{"key":"7120_CR51","first-page":"582","volume":"140","author":"MJ Boland","year":"2017","unstructured":"Boland, M. J. et al. Molecular analyses of neurogenic defects in a human pluripotent stem cell model of fragile X syndrome. Brain 140, 582\u2013598 (2017).","journal-title":"Brain"},{"key":"7120_CR52","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-30025-4","volume":"8","author":"N Sunamura","year":"2018","unstructured":"Sunamura, N., Iwashita, S., Enomoto, K., Kadoshima, T. & Isono, F. Loss of the fragile X mental retardation protein causes aberrant differentiation in human neural progenitor cells. Sci. Rep. 8, 11585 (2018).","journal-title":"Sci. Rep."},{"key":"7120_CR53","doi-asserted-by":"crossref","unstructured":"Gildin, L. et al. Impaired Functional Connectivity Underlies Fragile X Syndrome. Int. J. Mol. Sci. 23, 2048 (2022).","DOI":"10.3390\/ijms23042048"},{"key":"7120_CR54","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-020-00351-4","volume":"11","author":"S Das Sharma","year":"2020","unstructured":"Das Sharma, S. et al. Cortical neurons derived from human pluripotent stem cells lacking FMRP display altered spontaneous firing patterns. Mol. Autism 11, 52 (2020).","journal-title":"Mol. Autism"},{"key":"7120_CR55","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.1111\/ejn.14660","volume":"51","author":"JD Graef","year":"2020","unstructured":"Graef, J. D. et al. Partial FMRP expression is sufficient to normalize neuronal hyperactivity in Fragile X neurons. Eur. J. Neurosci. 51, 2143\u20132157 (2020).","journal-title":"Eur. J. Neurosci."},{"key":"7120_CR56","doi-asserted-by":"crossref","unstructured":"Zhang, Z. et al. The fragile X mutation impairs homeostatic plasticity in human neurons by blocking synaptic retinoic acid signaling. Sci. Transl. Med. 10, eaar4338 (2018).","DOI":"10.1126\/scitranslmed.aar4338"},{"key":"7120_CR57","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.ydbio.2020.09.012","volume":"468","author":"SG Susco","year":"2020","unstructured":"Susco, S. G. et al. FMR1 loss in a human stem cell model reveals early changes to intrinsic membrane excitability. Dev. Biol. 468, 93\u2013100 (2020).","journal-title":"Dev. Biol."},{"key":"7120_CR58","doi-asserted-by":"publisher","first-page":"15295","DOI":"10.1523\/JNEUROSCI.0317-15.2015","volume":"35","author":"M Telias","year":"2015","unstructured":"Telias, M., Kuznitsov-Yanovsky, L., Segal, M. & Ben-Yosef, D. Functional Deficiencies in Fragile X Neurons Derived from Human Embryonic Stem Cells. J. Neurosci. 35, 15295\u201315306 (2015).","journal-title":"J. Neurosci."},{"key":"7120_CR59","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1016\/j.cell.2018.01.012","volume":"172","author":"XS Liu","year":"2018","unstructured":"Liu, X. S. et al. Rescue of Fragile X Syndrome Neurons by DNA Methylation Editing of the FMR1 Gene. Cell 172, 979\u2013992.e6 (2018).","journal-title":"Cell"},{"key":"7120_CR60","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1007\/s11064-018-2694-5","volume":"44","author":"LA Williams","year":"2019","unstructured":"Williams, L. A. et al. Scalable Measurements of Intrinsic Excitability in Human iPS Cell-Derived Excitatory Neurons Using All-Optical Electrophysiology. Neurochem. Res. 44, 714\u2013725 (2019).","journal-title":"Neurochem. Res."},{"key":"7120_CR61","first-page":"11.20.1","volume":"2017","author":"CA Werley","year":"2017","unstructured":"Werley, C. A. et al. All-optical electrophysiology for disease modeling and pharmacological characterization of neurons. Curr. Protoc. Pharmacol. 2017, 11.20.1\u201311.20.24 (2017).","journal-title":"Curr. Protoc. Pharmacol."},{"key":"7120_CR62","doi-asserted-by":"crossref","unstructured":"Liu, P. W. et al. A phenotypic screening platform for chronic pain therapeutics using all-optical electrophysiology. Pain. 165, 922-940 (2024).","DOI":"10.1097\/j.pain.0000000000003090"},{"key":"7120_CR63","doi-asserted-by":"publisher","unstructured":"Williams, L. A. et al. Discovery of novel compounds and target mechanisms using a high throughput, multiparametric phenotypic screen in a human neuronal model of Tuberous Sclerosis. preprint at bioRxiv. https:\/\/doi.org\/10.1101\/2024.02.22.581652 (2024).","DOI":"10.1101\/2024.02.22.581652"},{"key":"7120_CR64","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/j.neuron.2013.05.029","volume":"78","author":"Y Zhang","year":"2013","unstructured":"Zhang, Y. et al. Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron 78, 785\u2013798 (2013).","journal-title":"Neuron"},{"key":"7120_CR65","doi-asserted-by":"publisher","first-page":"2509","DOI":"10.1016\/j.celrep.2018.04.066","volume":"23","author":"R Nehme","year":"2018","unstructured":"Nehme, R. et al. Combining NGN2 Programming with Developmental Patterning Generates Human Excitatory Neurons with NMDAR-Mediated Synaptic Transmission. Cell Rep. 23, 2509\u20132523 (2018).","journal-title":"Cell Rep."},{"key":"7120_CR66","doi-asserted-by":"publisher","first-page":"11284","DOI":"10.1073\/pnas.1305590110","volume":"110","author":"JP Ferreira","year":"2013","unstructured":"Ferreira, J. P., Overton, K. W. & Wang, C. L. Tuning gene expression with synthetic upstream open reading frames. Proc. Natl Acad. Sci. USA 110, 11284\u201311289 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"7120_CR67","doi-asserted-by":"publisher","first-page":"2112","DOI":"10.12688\/f1000research.11885.1","volume":"6","author":"A Rajaratnam","year":"2017","unstructured":"Rajaratnam, A. et al. Fragile X syndrome and fragile X-associated disorders. F1000Res. 6, 2112 (2017).","journal-title":"F1000Res."},{"key":"7120_CR68","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.neuroscience.2016.03.011","volume":"324","author":"S Jacobs","year":"2016","unstructured":"Jacobs, S., Cheng, C. & Doering, L. C. Hippocampal neuronal subtypes develop abnormal dendritic arbors in the presence of Fragile X astrocytes. Neuroscience 324, 202\u2013217 (2016).","journal-title":"Neuroscience"},{"key":"7120_CR69","doi-asserted-by":"publisher","unstructured":"Jacobs, S. & Doering, L. C. Astrocytes Prevent Abnormal Neuronal Development in the Fragile X Mouse. J. Neurosci. https:\/\/doi.org\/10.1523\/JNEUROSCI.5027-09.2010 (2010).","DOI":"10.1523\/JNEUROSCI.5027-09.2010"},{"key":"7120_CR70","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.722378","volume":"12","author":"E Verdura","year":"2021","unstructured":"Verdura, E. et al. Heterogeneity in Fragile X Syndrome Highlights the Need for Precision Medicine-Based Treatments. Front. Psychiatry 12, 722378 (2021).","journal-title":"Front. Psychiatry"},{"key":"7120_CR71","doi-asserted-by":"publisher","first-page":"245","DOI":"10.3389\/fncel.2014.00245","volume":"8","author":"CA Cea-Del Rio","year":"2014","unstructured":"Cea-Del Rio, C. A. & Huntsman, M. M. The contribution of inhibitory interneurons to circuit dysfunction in Fragile X Syndrome. Front. Cell Neurosci. 8, 245 (2014).","journal-title":"Front. Cell Neurosci."},{"key":"7120_CR72","doi-asserted-by":"publisher","first-page":"197491","DOI":"10.1155\/2012\/197491","volume":"2012","author":"C Cheng","year":"2012","unstructured":"Cheng, C., Sourial, M. & Doering, L. C. Astrocytes and developmental plasticity in fragile X. Neural Plast. 2012, 197491 (2012).","journal-title":"Neural Plast."},{"key":"7120_CR73","doi-asserted-by":"publisher","first-page":"5794","DOI":"10.1364\/BOE.8.005794","volume":"8","author":"CA Werley","year":"2017","unstructured":"Werley, C. A., Chien, M.-P. & Cohen, A. E. An ultrawidefield microscope for high-speed fluorescence imaging and targeted optogenetic stimulation. Biomed. Opt. Express 8, 5794 (2017).","journal-title":"Biomed. Opt. Express"},{"key":"7120_CR74","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/j.neuron.2009.08.009","volume":"63","author":"EA Mukamel","year":"2009","unstructured":"Mukamel, E. A., Nimmerjahn, A. & Schnitzer, M. J. Automated Analysis of Cellular Signals from Large-Scale Calcium Imaging Data. Neuron 63, 747\u2013760 (2009).","journal-title":"Neuron"},{"key":"7120_CR75","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1038\/nmeth.3000","volume":"11","author":"DR Hochbaum","year":"2014","unstructured":"Hochbaum, D. R. et al. All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins. Nat. Methods 11, 825\u2013833 (2014).","journal-title":"Nat. Methods"},{"key":"7120_CR76","first-page":"2825","volume":"12","author":"F Pedregosa","year":"2011","unstructured":"Pedregosa, F. et al. Scikit-learn: Machine Learning in Python. J. Mach. Learn. Res. 12, 2825\u20132830 (2011).","journal-title":"J. Mach. Learn. Res."},{"key":"7120_CR77","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v067.i01","volume":"67","author":"D Bates","year":"2015","unstructured":"Bates, D., M\u00e4chler, M., Bolker, B. & Walker, S. Fitting Linear Mixed-Effects Models Using lme4. J. Stat. Softw. 67, 1\u201348 (2015).","journal-title":"J. Stat. Softw."},{"key":"7120_CR78","unstructured":"Lenth, R. V. Emmeans: Estimated Marginal Means, Aka Least-Squares Means https:\/\/CRAN.Rproject.org\/package=emmeans (2021)."},{"key":"7120_CR79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v082.i13","volume":"82","author":"A Kuznetsova","year":"2017","unstructured":"Kuznetsova, A., Brockhoff, P. B. & Christensen, R. H. B. lmerTest Package: Tests in Linear Mixed Effects Models. J. Stat. Softw. 82, 1\u201326 (2017).","journal-title":"J. Stat. Softw."},{"key":"7120_CR80","unstructured":"L\u00fcdecke, D. sjPlot: Data Visualization for Statistics in Social Science https:\/\/CRAN.Rproject.org\/package=sjPlot (2022)."},{"key":"7120_CR81","doi-asserted-by":"publisher","unstructured":"Delaney-Busch, N. & Ryan, S. J. Fragile X Patient Phenotyping Code https:\/\/doi.org\/10.5281\/zenodo.13936561 (2024).","DOI":"10.5281\/zenodo.13936561"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-07120-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-07120-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-07120-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T17:04:48Z","timestamp":1730912688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-07120-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,6]]},"references-count":81,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["7120"],"URL":"https:\/\/doi.org\/10.1038\/s42003-024-07120-6","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,6]]},"assertion":[{"value":"12 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"J.J.F., K.H., S.J.R., J.J., J.G., L.A.W., and G.T.D. are current employees of Quiver Bioscience and may hold stock options in Quiver Bioscience. D.G. was an employee of Q-State Bioscience, is currently a consultant for Quiver Bioscience and has received stock options in Quiver Bioscience. E.N., C.F., M.B., B.F. are current employees of Vertex Pharmaceuticals Inc. and hold stock in Vertex Pharmaceuticals Inc. N.D.B. is a former employee of Q-State Biosciences and may be an inventor on relevant patents, but holds no financial stake, stock, or options. M.F.B. is a co-founder of Allos Pharma, and a consultant and owner of stock options for Addex Therapeutics and Luminopia. H.U. and H.S. are current employees of Wave Life Sciences and report stock ownership in Wave Life Sciences. R.P.D. was employed at Vertex Pharmaceuticals at the time of the study, is a current employee of Intellia Therapeutics, and reports stock ownership in Intellia Therapeutics. Elizabeth Berry-Kravis has received funding from Acadia, Alcobra, AMO, Asuragen, Avexis, Biogen, BioMarin, Cydan, Engrail, Erydel, Fulcrum, GeneTx, GW, Healx, Ionis, Jaguar, Kisbee, Lumos, Marinus, Moment Biosciences, Neuren, Neurogene, Neurotrope, Novartis, Orphazyme\/Kempharm, Ovid, PTC Therapeutics, Retrophin, Roche, Seaside Therapeutics, Taysha, Tetra, Ultragenyx, Yamo, Zynerba, and Vtesse\/Sucampo\/Mallinckrodt Pharmaceuticals, to consult on trial design or run clinical or lab validation trials in genetic neurodevelopmental or neurodegenerative disorders, all of which is directed to RUMC in support of rare disease programs; B.-K. receives no personal funds and RUMC has no relevant financial interest in any of the commercial entities listed.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1447"}}