{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T20:03:09Z","timestamp":1794513789812,"version":"4.9.1"},"reference-count":104,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T00:00:00Z","timestamp":1561420800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T00:00:00Z","timestamp":1561420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Genetic mutations of the Methyl-CpG-binding protein-2 (MECP2) gene underlie Rett syndrome (RTT). Developmental processes are often considered to be irrelevant in RTT pathogenesis but neuronal activity at birth has not been recorded. We report that the GABA developmental shift at birth is abolished in CA3 pyramidal neurons of Mecp2<jats:sup>\u2212\/y<\/jats:sup>mice and the glutamatergic\/GABAergic postsynaptic currents (PSCs) ratio is increased. Two weeks later, GABA exerts strong excitatory actions, the glutamatergic\/GABAergic PSCs ratio is enhanced, hyper-synchronized activity is present and metabotropic long-term depression (LTD) is impacted. One day before delivery, maternal administration of the NKCC1 chloride importer antagonist bumetanide restored these parameters but not respiratory or weight deficits, nor the onset of mortality. Results suggest that birth is a critical period in RTT with important alterations that can be attenuated by bumetanide raising the possibility of early treatment of the disorder.<\/jats:p>","DOI":"10.1038\/s41598-019-45635-9","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T21:52:50Z","timestamp":1561499570000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Early alterations in a mouse model of Rett syndrome: the GABA developmental shift is abolished at birth"],"prefix":"10.1038","volume":"9","author":[{"given":"N.","family":"Lozovaya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Nardou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Tyzio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1500-4285","authenticated-orcid":false,"given":"M.","family":"Chiesa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Pons-Bennaceur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Eftekhari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.-T.","family":"Bui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Billon-Grand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1661-2856","authenticated-orcid":false,"given":"J.","family":"Rasero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Bonifazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Guimond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7354-0559","authenticated-orcid":false,"given":"J.-L.","family":"Gaiarsa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7418-7873","authenticated-orcid":false,"given":"D. C.","family":"Ferrari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6208-8480","authenticated-orcid":false,"given":"Y.","family":"Ben-Ari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,6,25]]},"reference":[{"key":"45635_CR1","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/13810","volume":"23","author":"RE Amir","year":"1999","unstructured":"Amir, R. E. et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23, 185\u2013188 (1999).","journal-title":"Nat. Genet."},{"key":"45635_CR2","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1136\/jmg.2007.049452","volume":"44","author":"L Villard","year":"2007","unstructured":"Villard, L. MECP2 mutations in males. J. Med. Genet. 44, 417\u2013423 (2007).","journal-title":"J. Med. Genet."},{"key":"45635_CR3","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/S0014-5793(00)01994-3","volume":"481","author":"A Orrico","year":"2000","unstructured":"Orrico, A. et al. MECP2mutation in male patients with non-specific X-linked mental retardation. FEBS Lett. 481, 285\u2013288 (2000).","journal-title":"FEBS Lett."},{"key":"45635_CR4","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1086\/303078","volume":"67","author":"I Meloni","year":"2000","unstructured":"Meloni, I. et al. A mutation in the rett syndrome gene, MECP2, causes X-linked mental retardation and progressive spasticity in males. Am. J. Hum. Genet. 67, 982\u2013985 (2000).","journal-title":"Am. J. Hum. Genet."},{"key":"45635_CR5","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1002\/ana.22154","volume":"68","author":"AK Percy","year":"2010","unstructured":"Percy, A. K. et al. Rett syndrome diagnostic criteria: lessons from the Natural History Study. Ann. Neurol. 68, 951\u2013955 (2010).","journal-title":"Ann. Neurol."},{"key":"45635_CR6","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1038\/85899","volume":"27","author":"J Guy","year":"2001","unstructured":"Guy, J., Hendrich, B., Holmes, M., Martin, J. E. & Bird, A. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat. Genet. 27, 322\u2013326 (2001).","journal-title":"Nat. Genet."},{"key":"45635_CR7","doi-asserted-by":"publisher","first-page":"13612","DOI":"10.1523\/JNEUROSCI.1854-13.2013","volume":"33","author":"SK Garg","year":"2013","unstructured":"Garg, S. K. et al. Systemic Delivery of MeCP2 Rescues Behavioral and Cellular Deficits in Female Mouse Models of Rett Syndrome. Journal of Neuroscience 33, 13612\u201313620 (2013).","journal-title":"Journal of Neuroscience"},{"key":"45635_CR8","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1126\/science.1206593","volume":"333","author":"CM McGraw","year":"2011","unstructured":"McGraw, C. M., Samaco, R. C. & Zoghbi, H. Y. Adult neural function requires MeCP2. Science. 333, 186\u2013186 (2011).","journal-title":"Science."},{"issue":"Suppl 1","key":"45635_CR9","doi-asserted-by":"publisher","first-page":"S25","DOI":"10.1016\/j.braindev.2005.03.016","volume":"27","author":"C Trevarthen","year":"2005","unstructured":"Trevarthen, C. & Daniel, S. Disorganized rhythm and synchrony: early signs of autism and Rett syndrome. Brain Dev. 27(Suppl 1), S25\u2013S34 (2005).","journal-title":"Brain Dev."},{"key":"45635_CR10","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1016\/j.ridd.2013.01.014","volume":"34","author":"PB Marschik","year":"2013","unstructured":"Marschik, P. B. et al. Changing the perspective on early development of Rett syndrome. Research in Developmental Disabilities 34, 1236\u20131239 (2013).","journal-title":"Research in Developmental Disabilities"},{"issue":"1","key":"45635_CR11","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/1866-1955-6-20","volume":"6","author":"Jeffrey L Neul","year":"2014","unstructured":"Neul, J. L. et al. Developmental delay in Rett syndrome: data from the natural history study. 1\u20139, https:\/\/doi.org\/10.1186\/1866-1955-6-20 (2014).","journal-title":"Journal of Neurodevelopmental Disorders"},{"key":"45635_CR12","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/j.1469-8749.1998.tb15371.x","volume":"40","author":"H Leonard","year":"1998","unstructured":"Leonard, H. & Bower, C. Is the girl with Rett syndrome normal at birth? Dev.Med.Child Neurol. 40, 115\u2013121 (1998).","journal-title":"Dev.Med.Child Neurol."},{"key":"45635_CR13","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1203\/01.PDR.0000155945.94249.0A","volume":"57","author":"C Einspieler","year":"2005","unstructured":"Einspieler, C., Kerr, A. M. & Prechtl, H. F. R. Is the Early Development of Girls with Rett Disorder Really Normal? Pediatr. Res. 57, 696\u2013700 (2005).","journal-title":"Pediatr. Res."},{"key":"45635_CR14","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1007\/s10354-016-0498-2","volume":"166","author":"C Einspieler","year":"2016","unstructured":"Einspieler, C., Freilinger, M. & Marschik, P. B. Behavioural biomarkers of typical Rett syndrome: moving towards early identification. Wien Med Wochenschr 166, 333\u2013337 (2016).","journal-title":"Wien Med Wochenschr"},{"key":"45635_CR15","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/j.1601-183X.2009.00551.x","volume":"9","author":"B De Filippis","year":"2010","unstructured":"De Filippis, B., Ricceri, L. & Laviola, G. Early postnatal behavioral changes in the Mecp2-308 truncation mouse model of Rett syndrome. Genes, Brain and Behavior 9, 213\u2013223 (2010).","journal-title":"Genes, Brain and Behavior"},{"key":"45635_CR16","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/scientificamerican0486-100","volume":"254","author":"H Lagercrantz","year":"1986","unstructured":"Lagercrantz, H. & Slotkin, T. A. The \u2018Stress\u2019 of Being Born. Scientific American 254, 100\u2013107 (1986).","journal-title":"Scientific American"},{"key":"45635_CR17","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/j.clp.2012.09.009","volume":"39","author":"NH Hillman","year":"2012","unstructured":"Hillman, N. H., Kallapur, S. G. & Jobe, A. H. Physiology of Transition from Intrauterine to Extrauterine Life. Clinics in Perinatology 39, 769\u2013783 (2012).","journal-title":"Clinics in Perinatology"},{"key":"45635_CR18","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/1465-9921-10-124","volume":"10","author":"NH Hillman","year":"2009","unstructured":"Hillman, N. H. et al. Antenatal and postnatal corticosteroid and resuscitation induced lung injury in preterm sheep. Respir. Res. 10, 124 (2009).","journal-title":"Respir. Res."},{"key":"45635_CR19","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1038\/pr.2015.21","volume":"77","author":"SB Hooper","year":"2015","unstructured":"Hooper, S. B. et al. Cardiovascular transition at birth: a physiological sequence. Pediatr. Res. 77, 608\u2013614 (2015).","journal-title":"Pediatr. Res."},{"key":"45635_CR20","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1016\/j.cell.2018.06.045","volume":"174","author":"A Olin","year":"2018","unstructured":"Olin, A. et al. Stereotypic Immune System Development in Newborn Children. Cell 174, 1277\u20131292.e14 (2018).","journal-title":"Cell"},{"key":"45635_CR21","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-018-0599-1","volume":"10","author":"S Schaffert","year":"2018","unstructured":"Schaffert, S. & Khatri, P. Early life immunity in the era of systems biology: understanding development and disease. Genome Med 10, 88 (2018).","journal-title":"Genome Med"},{"key":"45635_CR22","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/j.alit.2017.07.010","volume":"66","author":"M Tanaka","year":"2017","unstructured":"Tanaka, M. & Nakayama, J. Development of the gut microbiota in infancy and its impact on health in later life. Allergol Int 66, 515\u2013522 (2017).","journal-title":"Allergol Int"},{"key":"45635_CR23","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/nrn3956","volume":"16","author":"Y Ben-Ari","year":"2015","unstructured":"Ben-Ari, Y. Is birth a critical period in the pathogenesis of autism spectrum disorders? Nat. Rev. Neurosci. 16, 498\u2013505 (2015).","journal-title":"Nat. Rev. Neurosci."},{"key":"45635_CR24","doi-asserted-by":"crossref","unstructured":"Curran, E. A. et al. Association Between Obstetric Mode of Delivery and Autism Spectrum Disorder: A Population-Based Sibling Design Study. JAMA Psychiatry (2015).","DOI":"10.1001\/jamapsychiatry.2015.0846"},{"key":"45635_CR25","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1001\/jamapsychiatry.2013.2107","volume":"70","author":"BM D\u2019Onofrio","year":"2013","unstructured":"D\u2019Onofrio, B. M. et al. Preterm birth and mortality and morbidity: a population-based quasi-experimental study. JAMA Psychiatry 70, 1231\u20131240 (2013).","journal-title":"JAMA Psychiatry"},{"key":"45635_CR26","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1001\/archpsyc.61.6.618","volume":"61","author":"EJ Glasson","year":"2004","unstructured":"Glasson, E. J. et al. Perinatal factors and the development of autism: a population study. Arch Gen Psychiatry 61, 618\u2013627 (2004).","journal-title":"Arch Gen Psychiatry"},{"key":"45635_CR27","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1007\/s10803-009-0903-4","volume":"40","author":"JR Mann","year":"2009","unstructured":"Mann, J. R., McDermott, S., Bao, H., Hardin, J. & Gregg, A. Pre-Eclampsia, Birth Weight, and Autism Spectrum Disorders. J Autism Dev Disord 40, 548\u2013554 (2009).","journal-title":"J Autism Dev Disord"},{"key":"45635_CR28","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1002\/aur.228","volume":"5","author":"K Lyall","year":"2011","unstructured":"Lyall, K., Pauls, D. L., Spiegelman, D., Ascherio, A. & Santangelo, S. L. Pregnancy complications and obstetric suboptimality in association with autism spectrum disorders in children of the nurses\u2019 health study II. Autism Res 5, 21\u201330 (2011).","journal-title":"Autism Res"},{"key":"45635_CR29","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s10995-006-0142-7","volume":"11","author":"M Brimacombe","year":"2006","unstructured":"Brimacombe, M., Ming, X. & Lamendola, M. Prenatal and Birth Complications in Autism. Matern Child Health J 11, 73\u201379 (2006).","journal-title":"Matern Child Health J"},{"key":"45635_CR30","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.1126\/science.1133212","volume":"314","author":"R Tyzio","year":"2006","unstructured":"Tyzio, R. et al. Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery. Science. 314, 1788\u20131792 (2006).","journal-title":"Science."},{"key":"45635_CR31","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1126\/science.1247190","volume":"343","author":"R Tyzio","year":"2014","unstructured":"Tyzio, R. et al. Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring. Science. 343, 675\u2013679 (2014).","journal-title":"Science."},{"key":"45635_CR32","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1126\/science.1256009","volume":"346","author":"S Eftekhari","year":"2014","unstructured":"Eftekhari, S. et al. Response to Comment on \u2018Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring\u2019. Science. 346, 176\u2013176 (2014).","journal-title":"Science."},{"key":"45635_CR33","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.nbd.2015.02.015","volume":"77","author":"GL Holmes","year":"2015","unstructured":"Holmes, G. L. et al. Alterations in sociability and functional brain connectivity caused by early-life seizures are prevented by bumetanide. Neurobiol.Dis. 77, 204\u2013219 (2015).","journal-title":"Neurobiol.Dis."},{"key":"45635_CR34","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1523\/JNEUROSCI.4447-13.2014","volume":"34","author":"Q He","year":"2014","unstructured":"He, Q., Nomura, T., Xu, J. & Contractor, A. The developmental switch in GABA polarity is delayed in fragile X mice. Journal of Neuroscience 34, 446\u2013450 (2014).","journal-title":"Journal of Neuroscience"},{"key":"45635_CR35","doi-asserted-by":"crossref","unstructured":"Banerjee, A. et al. Jointly reduced inhibition and excitation underlies circuit-wide changes in cortical processing in Rett syndrome. Proc. Natl. Acad. Sci. USA (2016).","DOI":"10.1073\/pnas.1615330113"},{"key":"45635_CR36","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1152\/physrev.00017.2006","volume":"87","author":"Y Ben-Ari","year":"2007","unstructured":"Ben-Ari, Y., Gaiarsa, J.-L., Tyzio, R. & Khazipov, R. GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations. Physiol. Rev. 87, 1215\u20131284 (2007).","journal-title":"Physiol. Rev."},{"key":"45635_CR37","doi-asserted-by":"publisher","first-page":"E1618","DOI":"10.1073\/pnas.1716871115","volume":"115","author":"Z Dargaei","year":"2018","unstructured":"Dargaei, Z. et al. Restoring GABAergic inhibition rescues memory deficits in a Huntington\u2019s disease mouse model. Proc.Natl.Acad.Sci.USA 115, E1618\u2013E1626 (2018).","journal-title":"Proc.Natl.Acad.Sci.USA"},{"key":"45635_CR38","doi-asserted-by":"publisher","first-page":"185","DOI":"10.7554\/eLife.31451","volume":"7","author":"SE Kee","year":"2018","unstructured":"Kee, S. E., Mou, X., Zoghbi, H. Y. & Ji, D. Impaired spatial memory codes in a mouse model of Rett syndrome. eLife 7, 185 (2018).","journal-title":"eLife"},{"key":"45635_CR39","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.neuron.2016.07.018","volume":"91","author":"H Lu","year":"2016","unstructured":"Lu, H. et al. Loss and Gain of MeCP2 Cause Similar Hippocampal Circuit Dysfunction that Is Rescued by Deep Brain Stimulation in a Rett Syndrome Mouse Model. Neuron 91, 739\u2013747 (2016).","journal-title":"Neuron"},{"key":"45635_CR40","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.nbd.2005.07.005","volume":"21","author":"Y Asaka","year":"2006","unstructured":"Asaka, Y., Jugloff, D. G. M., Zhang, L., Eubanks, J. H. & Fitzsimonds, R. M. Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome. Neurobiology of Disease 21, 217\u2013227 (2006).","journal-title":"Neurobiology of Disease"},{"key":"45635_CR41","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1523\/JNEUROSCI.2623-05.2006","volume":"26","author":"P Moretti","year":"2006","unstructured":"Moretti, P. et al. Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome. Journal of Neuroscience 26, 319\u2013327 (2006).","journal-title":"Journal of Neuroscience"},{"key":"45635_CR42","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1093\/hmg\/ddw074","volume":"25","author":"A Ghoshal","year":"2016","unstructured":"Ghoshal, A. et al. mGlu 5positive allosteric modulation normalizes synaptic plasticity defects and motor phenotypes in a mouse model of Rett syndrome. Hum. Mol. Genet. 25, 1990\u20132004 (2016).","journal-title":"Hum. Mol. Genet."},{"key":"45635_CR43","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.resp.2009.04.017","volume":"168","author":"DM Katz","year":"2009","unstructured":"Katz, D. M., Dutschmann, M., Ramirez, J.-M. & Hilaire, G. Breathing disorders in Rett syndrome: Progressive neurochemical dysfunction in the respiratory network after birth. Respir Physiol Neurobiol 168, 101\u2013108 (2009).","journal-title":"Respir Physiol Neurobiol"},{"key":"45635_CR44","first-page":"C895","volume":"311","author":"CM Johnson","year":"2016","unstructured":"Johnson, C. M. et al. Defects in brainstem neurons associated with breathing and motor function in the Mecp2R168X\/Y mouse model of Rett syndrome. AJP: Cell Physiology 311, C895\u2013C909 (2016).","journal-title":"AJP: Cell Physiology"},{"key":"45635_CR45","doi-asserted-by":"publisher","first-page":"11521","DOI":"10.1523\/JNEUROSCI.4373-05.2005","volume":"25","author":"J-C Viemari","year":"2005","unstructured":"Viemari, J.-C. et al. Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice. Journal of Neuroscience 25, 11521\u201311530 (2005).","journal-title":"Journal of Neuroscience"},{"key":"45635_CR46","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2017.101","volume":"7","author":"E Lemonnier","year":"2017","unstructured":"Lemonnier, E. et al. Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders. Transl Psychiatry 7, e1124 (2017).","journal-title":"Transl Psychiatry"},{"issue":"Suppl 1","key":"45635_CR47","doi-asserted-by":"publisher","first-page":"S35","DOI":"10.1016\/j.braindev.2005.03.017","volume":"27","author":"Y Nomura","year":"2005","unstructured":"Nomura, Y. Early behavior characteristics and sleep disturbance in Rett syndrome. Brain Dev. 27(Suppl 1), S35\u2013S42 (2005).","journal-title":"Brain Dev."},{"key":"45635_CR48","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1111\/j.1399-0004.2008.01005.x","volume":"74","author":"B Sch\u00fcle","year":"2008","unstructured":"Sch\u00fcle, B., Armstrong, D. D., Vogel, H., Oviedo, A. & Francke, U. Severe congenital encephalopathy caused by MECP2 null mutations in males: central hypoxia and reduced neuronal dendritic structure. Clin. Genet. 74, 116\u2013126 (2008).","journal-title":"Clin. Genet."},{"key":"45635_CR49","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.gene.2014.06.012","volume":"546","author":"F Fu","year":"2014","unstructured":"Fu, F. et al. Prenatal diagnosis of foetuses with congenital abnormalities and duplication of the MECP2 region. Gene 546, 222\u2013225 (2014).","journal-title":"Gene"},{"key":"45635_CR50","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.brainres.2010.08.090","volume":"1360","author":"Y Okabe","year":"2010","unstructured":"Okabe, Y. et al. Neural development of methyl-CpG-binding protein 2 null embryonic stem cells: a system for studying Rett syndrome. Brain Res. 1360, 17\u201327 (2010).","journal-title":"Brain Res."},{"key":"45635_CR51","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.cell.2010.10.016","volume":"143","author":"MCN Marchetto","year":"2010","unstructured":"Marchetto, M. C. N. et al. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143, 527\u2013539 (2010).","journal-title":"Cell"},{"key":"45635_CR52","doi-asserted-by":"publisher","first-page":"14169","DOI":"10.1073\/pnas.1018979108","volume":"108","author":"K-Y Kim","year":"2011","unstructured":"Kim, K.-Y., Hysolli, E. & Park, I.-H. Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome. Proc. Natl. Acad. Sci. USA 108, 14169\u201314174 (2011).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"45635_CR53","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.nbd.2014.03.009","volume":"67","author":"P Petazzi","year":"2014","unstructured":"Petazzi, P. et al. An increase in MECP2 dosage impairs neural tube formation. Neurobiol. Dis. 67, 49\u201356 (2014).","journal-title":"Neurobiol. Dis."},{"key":"45635_CR54","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.expneurol.2009.05.001","volume":"219","author":"K Tsujimura","year":"2009","unstructured":"Tsujimura, K., Abematsu, M., Kohyama, J., Namihira, M. & Nakashima, K. Neuronal differentiation of neural precursor cells is promoted by the methyl-CpG-binding protein MeCP2. Exp. Neurol. 219, 104\u2013111 (2009).","journal-title":"Exp. Neurol."},{"issue":"6","key":"45635_CR55","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.1093\/cercor\/bhv078","volume":"26","author":"Francesco Bedogni","year":"2015","unstructured":"Bedogni, F. et al. Defects During Mecp2 Null Embryonic Cortex Development Precede the Onset of Overt Neurological Symptoms. Cereb. Cortex, https:\/\/doi.org\/10.1093\/cercor\/bhv078 (2015).","journal-title":"Cerebral Cortex"},{"key":"45635_CR56","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1002\/dneu.22498","volume":"77","author":"K Nozawa","year":"2017","unstructured":"Nozawa, K. et al. Zebrafish Mecp2 is required for proper axonal elongation of motor neurons and synapse formation. Dev Neurobiol 77, 1101\u20131113 (2017).","journal-title":"Dev Neurobiol"},{"key":"45635_CR57","doi-asserted-by":"publisher","first-page":"214","DOI":"10.7554\/eLife.19374","volume":"5","author":"C Sampathkumar","year":"2016","unstructured":"Sampathkumar, C. et al. Loss of MeCP2 disrupts cell autonomous and autocrine BDNF signaling in mouse glutamatergic neurons. eLife 5, 214 (2016).","journal-title":"eLife"},{"key":"45635_CR58","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1093\/cercor\/bhx360","volume":"28","author":"C Cobolli Gigli","year":"2018","unstructured":"Cobolli Gigli, C. et al. Lack of Methyl-CpG Binding Protein 2 (MeCP2) Affects Cell Fate Refinement During Embryonic Cortical Development. Cereb. Cortex 28, 1846\u20131856 (2018).","journal-title":"Cereb. Cortex"},{"key":"45635_CR59","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1152\/jn.00826.2007","volume":"99","author":"L Medrihan","year":"2007","unstructured":"Medrihan, L. et al. Early Defects of GABAergic Synapses in the Brain Stem of a MeCP2 Mouse Model of Rett Syndrome. J. Neurophysiol. 99, 112\u2013121 (2007).","journal-title":"J. Neurophysiol."},{"key":"45635_CR60","doi-asserted-by":"publisher","first-page":"2470","DOI":"10.1152\/jn.00601.2009","volume":"103","author":"ZW Zhang","year":"2010","unstructured":"Zhang, Z. W., Zak, J. D. & Liu, H. MeCP2 Is Required for Normal Development of GABAergic Circuits in the Thalamus. J. Neurophysiol. 103, 2470\u20132481 (2010).","journal-title":"J. Neurophysiol."},{"key":"45635_CR61","first-page":"e1447","volume":"130","author":"A Fernandez","year":"2018","unstructured":"Fernandez, A. et al. The GABA Developmental Shift Is Abolished by Maternal Immune Activation Already at Birth. Cereb. Cortex 130, e1447 (2018).","journal-title":"Cereb. Cortex"},{"key":"45635_CR62","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/j.biopsych.2017.09.030","volume":"83","author":"I Corradini","year":"2018","unstructured":"Corradini, I. et al. Maternal Immune Activation Delays Excitatory-to-Inhibitory Gamma-Aminobutyric Acid Switch in Offspring. Biol. Psychiatry 83, 680\u2013691 (2018).","journal-title":"Biol. Psychiatry"},{"key":"45635_CR63","doi-asserted-by":"publisher","first-page":"e68851","DOI":"10.1371\/journal.pone.0068851","volume":"8","author":"ST Duarte","year":"2013","unstructured":"Duarte, S. T. et al. Abnormal Expression of Cerebrospinal Fluid Cation Chloride Cotransporters in Patients with Rett Syndrome. PLoS ONE 8, e68851 (2013).","journal-title":"PLoS ONE"},{"key":"45635_CR64","doi-asserted-by":"crossref","unstructured":"Tang, X. et al. KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome. Proc. Natl. Acad. Sci. USA (2016).","DOI":"10.1073\/pnas.1524013113"},{"key":"45635_CR65","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1126\/science.1090842","volume":"302","author":"K Martinowich","year":"2003","unstructured":"Martinowich, K. et al. DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science. 302, 890\u2013893 (2003).","journal-title":"Science."},{"key":"45635_CR66","first-page":"172","volume":"8","author":"X Xu","year":"2014","unstructured":"Xu, X., Miller, E. C. & Pozzo-Miller, L. Dendritic spine dysgenesis in Rett syndrome. Front. Neuroanat. 8, 172 (2014).","journal-title":"Front. Neuroanat."},{"key":"45635_CR67","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.neuron.2005.12.027","volume":"49","author":"Q Chang","year":"2006","unstructured":"Chang, Q., Khare, G., Dani, V., Nelson, S. & Jaenisch, R. The Disease Progression of Mecp2 Mutant Mice Is Affected by the Level of BDNF Expression. Neuron 49, 341\u2013348 (2006).","journal-title":"Neuron"},{"issue":"Pt 2","key":"45635_CR68","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1111\/j.1469-7793.1998.527bk.x","volume":"510","author":"A Balkowiec","year":"1998","unstructured":"Balkowiec, A. & Katz, D. M. Brain-derived neurotrophic factor is required for normal development of the central respiratory rhythm in mice. J. Physiol. (Lond.) 510(Pt 2), 527\u2013533 (1998).","journal-title":"J. Physiol. (Lond.)"},{"key":"45635_CR69","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1242\/dmm.016030","volume":"7","author":"M Kron","year":"2014","unstructured":"Kron, M. et al. A BDNF loop-domain mimetic acutely reverses spontaneous apneas and respiratory abnormalities during behavioral arousal in a mouse model of Rett syndrome. Disease Models & Mechanisms 7, 1047\u20131055 (2014).","journal-title":"Disease Models & Mechanisms"},{"key":"45635_CR70","doi-asserted-by":"publisher","first-page":"7234","DOI":"10.1523\/JNEUROSCI.1943-07.2007","volume":"27","author":"K Kohara","year":"2007","unstructured":"Kohara, K. et al. A local reduction in cortical GABAergic synapses after a loss of endogenous brain-derived neurotrophic factor, as revealed by single-cell gene knock-out method. Journal of Neuroscience 27, 7234\u20137244 (2007).","journal-title":"Journal of Neuroscience"},{"key":"45635_CR71","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1038\/nrn988","volume":"3","author":"C Vicario-Abej\u00f3n","year":"2002","unstructured":"Vicario-Abej\u00f3n, C., Owens, D., McKay, R. & Segal, M. Role of neurotrophins in central synapse formation and stabilization. Nat. Rev. Neurosci. 3, 965\u2013974 (2002).","journal-title":"Nat. Rev. Neurosci."},{"key":"45635_CR72","doi-asserted-by":"publisher","first-page":"273","DOI":"10.3389\/fncel.2018.00273","volume":"12","author":"C Porcher","year":"2018","unstructured":"Porcher, C., Medina, I. & Gaiarsa, J.-L. Mechanism of BDNF Modulation in GABAergic Synaptic Transmission in Healthy and Disease Brains. Front Cell Neurosci 12, 273 (2018).","journal-title":"Front Cell Neurosci"},{"key":"45635_CR73","doi-asserted-by":"publisher","first-page":"18400","DOI":"10.1074\/jbc.M115.650465","volume":"290","author":"W Zhong","year":"2015","unstructured":"Zhong, W. et al. Methyl CpG Binding Protein 2 Gene Disruption Augments Tonic Currents of \u03b3-Aminobutyric Acid Receptors in Locus Coeruleus Neurons: IMPACT ON NEURONAL EXCITABILITY AND BREATHING. J.Biol.Chem. 290, 18400\u201318411 (2015).","journal-title":"J.Biol.Chem."},{"key":"45635_CR74","first-page":"C844","volume":"304","author":"X Jin","year":"2013","unstructured":"Jin, X., Cui, N., Zhong, W., Jin, X.-T. & Jiang, C. GABAergic synaptic inputs of locus coeruleus neurons in wild-type and Mecp2-null mice. AJP: Cell Physiology 304, C844\u201357 (2013).","journal-title":"AJP: Cell Physiology"},{"key":"45635_CR75","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.resp.2011.02.002","volume":"177","author":"N Voituron","year":"2011","unstructured":"Voituron, N. & Hilaire, G. The benzodiazepine Midazolam mitigates the breathing defects of Mecp2-deficient mice. Respir Physiol Neurobiol 177, 56\u201360 (2011).","journal-title":"Respir Physiol Neurobiol"},{"key":"45635_CR76","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1007\/s13311-015-0343-0","volume":"12","author":"D Ma","year":"2015","unstructured":"Ma, D. et al. Rescue of Methyl-CpG Binding Protein 2 Dysfunction-induced Defects in Newborn Neurons by Pentobarbital. Neurotherapeutics 12, 477\u2013490 (2015).","journal-title":"Neurotherapeutics"},{"key":"45635_CR77","doi-asserted-by":"publisher","first-page":"2754","DOI":"10.1523\/JNEUROSCI.4900-12.2014","volume":"34","author":"W Zhang","year":"2014","unstructured":"Zhang, W., Peterson, M., Beyer, B., Frankel, W. N. & Zhang, Z.-W. Loss of MeCP2 from forebrain excitatory neurons leads to cortical hyperexcitation and seizures. Journal of Neuroscience 34, 2754\u20132763 (2014).","journal-title":"Journal of Neuroscience"},{"key":"45635_CR78","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1002\/hipo.20389","volume":"18","author":"L Zhang","year":"2008","unstructured":"Zhang, L., He, J., Jugloff, D. G. M. & Eubanks, J. H. The MeCP2-null mouse hippocampus displays altered basal inhibitory rhythms and is prone to hyperexcitability. Hippocampus. 18, 294\u2013309 (2008).","journal-title":"Hippocampus."},{"key":"45635_CR79","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/nature09582","volume":"468","author":"HT Chao","year":"2010","unstructured":"Chao, H. T. et al. Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes1. Nature 468, 263\u2013269 (2010).","journal-title":"Nature"},{"key":"45635_CR80","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1002\/hipo.22360","volume":"25","author":"G Calfa","year":"2015","unstructured":"Calfa, G., Li, W., Rutherford, J. M. & Pozzo-Miller, L. Excitation\/inhibition imbalance and impaired synaptic inhibition in hippocampal area CA3 of Mecp2 knockout mice. Hippocampus. 25, 159\u2013168 (2015).","journal-title":"Hippocampus."},{"key":"45635_CR81","doi-asserted-by":"publisher","first-page":"E1575","DOI":"10.1073\/pnas.1517244113","volume":"113","author":"W Li","year":"2016","unstructured":"Li, W., Xu, X. & Pozzo-Miller, L. Excitatory synapses are stronger in the hippocampus of Rett syndrome mice due to altered synaptic trafficking of AMPA-type glutamate receptors. Proc. Natl. Acad. Sci. USA 113, E1575\u201384 (2016).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"45635_CR82","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1017\/S1461145712001216","volume":"16","author":"A Banerjee","year":"2013","unstructured":"Banerjee, A. et al. Impairment of cortical GABAergic synaptic transmission in an environmental rat model of autism. Int. J. Neuropsychopharmacol. 16, 1309\u20131318 (2013).","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"45635_CR83","doi-asserted-by":"publisher","first-page":"12560","DOI":"10.1073\/pnas.0506071102","volume":"102","author":"VS Dani","year":"2005","unstructured":"Dani, V. S. et al. Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett syndrome. Proc.Natl.Acad.Sci.USA 102, 12560\u201312565 (2005).","journal-title":"Proc.Natl.Acad.Sci.USA"},{"key":"45635_CR84","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.ajpath.2013.03.019","volume":"183","author":"C Bodda","year":"2013","unstructured":"Bodda, C. et al. Mild overexpression of Mecp2 in mice causes a higher susceptibility toward seizures. Am. J. Pathol. 183, 195\u2013210 (2013).","journal-title":"Am. J. Pathol."},{"key":"45635_CR85","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1111\/j.1528-1167.2010.02597.x","volume":"51","author":"A Nissenkorn","year":"2010","unstructured":"Nissenkorn, A. et al. Epilepsy in Rett syndrome\u2013the experience of a National Rett Center. Epilepsia 51, 1252\u20131258 (2010).","journal-title":"Epilepsia"},{"key":"45635_CR86","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6036","volume":"5","author":"L-J He","year":"2014","unstructured":"He, L.-J. et al. Conditional deletion of Mecp2 in parvalbumin-expressing GABAergic cells results in the absence of critical period plasticity. Nat Commun 5, 5036 (2014).","journal-title":"Nat Commun"},{"key":"45635_CR87","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.neuron.2015.10.029","volume":"88","author":"A Ito-Ishida","year":"2015","unstructured":"Ito-Ishida, A., Ure, K., Chen, H., Swann, J. W. & Zoghbi, H. Y. Loss of MeCP2 in Parvalbumin-and Somatostatin-Expressing Neurons in Mice Leads to Distinct Rett Syndrome-like Phenotypes. Neuron 88, 651\u2013658 (2015).","journal-title":"Neuron"},{"issue":"Pt 3","key":"45635_CR88","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1111\/j.1469-7793.1998.761bg.x","volume":"511","author":"S Otani","year":"1998","unstructured":"Otani, S. & Connor, J. A. Requirement of rapid Ca2+\u2009entry and synaptic activation of metabotropic glutamate receptors for the induction of long-term depression in adult rat hippocampus. J Physiol (Lond) 511(Pt 3), 761\u2013770 (1998).","journal-title":"J Physiol (Lond)"},{"key":"45635_CR89","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1016\/S0028-3908(97)00181-0","volume":"36","author":"MJ Palmer","year":"1997","unstructured":"Palmer, M. J., Irving, A. J., Seabrook, G. R., Jane, D. E. & Collingridge, G. L. The group I mGlu receptor agonist DHPG induces a novel form of LTD in the CA1 region of the hippocampus. Neuropharmacology 36, 1517\u20131532 (1997).","journal-title":"Neuropharmacology"},{"key":"45635_CR90","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1016\/S0896-6273(00)80336-0","volume":"18","author":"SH Oliet","year":"1997","unstructured":"Oliet, S. H., Malenka, R. C. & Nicoll, R. A. Two distinct forms of long-term depression coexist in CA1 hippocampal pyramidal cells. Neuron 18, 969\u2013982 (1997).","journal-title":"Neuron"},{"key":"45635_CR91","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1038\/nm.3827","volume":"21","author":"G Deidda","year":"2015","unstructured":"Deidda, G. et al. Reversing excitatory GABAAR signaling restores synaptic plasticity and memory in a mouse model of Down syndrome. Nat Med 21, 318\u2013326 (2015).","journal-title":"Nat Med"},{"key":"45635_CR92","doi-asserted-by":"publisher","first-page":"3019","DOI":"10.1111\/j.1460-9568.2004.03806.x","volume":"20","author":"I Pavlov","year":"2004","unstructured":"Pavlov, I., Riekki, R. & Taira, T. Synergistic action of GABA-A and NMDA receptors in the induction of long-term depression in glutamatergic synapses in the newborn rat hippocampus. Eur J Neurosci 20, 3019\u20133026 (2004).","journal-title":"Eur J Neurosci"},{"key":"45635_CR93","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1159\/000244492","volume":"72","author":"AM Lopez-Samblas","year":"1997","unstructured":"Lopez-Samblas, A. M., Adams, J. A., Goldberg, R. N. & Modi, M. W. The pharmacokinetics of bumetanide in the newborn infant. Biol. Neonate 72, 265\u2013272 (1997).","journal-title":"Biol. Neonate"},{"key":"45635_CR94","first-page":"45","volume":"6","author":"Y Ben-Ari","year":"2012","unstructured":"Ben-Ari, Y. The Yin and Yen of GABA in Brain Development and Operation in Health and Disease. Front. Cell Neurosci. 6, 45 (2012).","journal-title":"Front. Cell Neurosci."},{"key":"45635_CR95","doi-asserted-by":"crossref","unstructured":"Melchior, M. et al. Pharmacological rescue of nociceptive hypersensitivity and oxytocin analgesia impairment in a rat model of neonatal maternal separation. Pain 1 (2018).","DOI":"10.1097\/j.pain.0000000000001375"},{"key":"45635_CR96","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3389\/fncel.2011.00003","volume":"5","author":"M Mazzuca","year":"2011","unstructured":"Mazzuca, M. et al. Newborn Analgesia Mediated by Oxytocin during Delivery. Front Cell Neurosci 5, 3 (2011).","journal-title":"Front Cell Neurosci"},{"key":"45635_CR97","doi-asserted-by":"crossref","unstructured":"Meziane, H. et al. An Early Postnatal Oxytocin Treatment Prevents Social and Learning Deficits in Adult Mice Deficient for Magel2, a Gene Involved in Prader-Willi Syndrome and Autism. Biol. Psychiatry (2014).","DOI":"10.1016\/j.biopsych.2014.11.010"},{"key":"45635_CR98","doi-asserted-by":"publisher","first-page":"4895","DOI":"10.1093\/hmg\/ddq424","volume":"19","author":"F Schaller","year":"2010","unstructured":"Schaller, F. et al. A single postnatal injection of oxytocin rescues the lethal feeding behaviour in mouse newborns deficient for the imprinted Magel2 gene. Hum. Mol. Genet. 19, 4895\u20134905 (2010).","journal-title":"Hum. Mol. Genet."},{"key":"45635_CR99","doi-asserted-by":"crossref","unstructured":"Muscatelli, F., Desarmenien, M. G., Matarazzo, V. & Grinevich, V. Oxytocin Signaling in the Early Life of Mammals: Link to Neurodevelopmental Disorders Associated with ASD. Curr Top Behav Neurosci (2017).","DOI":"10.1007\/7854_2017_16"},{"key":"45635_CR100","doi-asserted-by":"publisher","first-page":"e20162976","DOI":"10.1542\/peds.2016-2976","volume":"139","author":"M Tauber","year":"2017","unstructured":"Tauber, M. et al. The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader-Willi Syndrome. PEDIATRICS 139, e20162976 (2017).","journal-title":"PEDIATRICS"},{"key":"45635_CR101","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.devcel.2013.09.002","volume":"27","author":"T Toda","year":"2013","unstructured":"Toda, T. et al. Birth Regulates the Initiation of Sensory Map Formation through Serotonin Signaling. Dev. Cell 27, 32\u201346 (2013).","journal-title":"Dev. Cell"},{"key":"45635_CR102","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6606-7-8","volume":"7","author":"T Toda","year":"2014","unstructured":"Toda, T. & Kawasaki, H. The development of suckling behavior of neonatal mice is regulated by birth. Molecular Brain 7, 8 (2014).","journal-title":"Molecular Brain"},{"key":"45635_CR103","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676\u2013682 (2012).","journal-title":"Nat. Methods"},{"key":"45635_CR104","unstructured":"Bulletin, N. C. P. Dominance statistics: Ordinal analyses to answer ordinal questions. psycnet.apa.org (1993)."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45635-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45635-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45635-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T06:40:00Z","timestamp":1721457600000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45635-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,25]]},"references-count":104,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["45635"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-45635-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,25]]},"assertion":[{"value":"14 February 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"N.L., R.N., R.T., M.C., S.E., T.-T.B., D.G., D.C.F. and Y.B.-A. are or were paid by Neurochlore, a biotech company dedicated to the development of treatments for children with autism. N.L., R.N., R.T., D.C.F. and Y.B.-A. are shareholders of Neurochlore. Y.B.-A. is CEO of Neurochlore.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"9276"}}