{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:26:34Z","timestamp":1791293194336,"version":"4.1.0"},"reference-count":64,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T00:00:00Z","timestamp":1515456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T00:00:00Z","timestamp":1515456000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T00:00:00Z","timestamp":1515456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD081037"],"award-info":[{"award-number":["HD081037"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rett Syndrome Research Trust","award":["RSRT"],"award-info":[{"award-number":["RSRT"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Studies linking mutations in Methyl CpG Binding Protein 2 (MeCP2) to physiological defects in the neurological disease, Rett syndrome, have focused largely upon neuronal dysfunction despite MeCP2 ubiquitous expression. Here we explore roles for astrocytes in neuronal network function using cortical slice recordings. We find that astrocyte stimulation in wild-type mice increases excitatory synaptic activity that is absent in male mice lacking MeCP2 globally. To determine the cellular basis of the defect, we exploit a female mouse model for Rett syndrome that expresses wild-type MeCP2-GFP in a mosaic distribution throughout the brain, allowing us to test all combinations of wild-type and mutant cells. We find that the defect is dependent upon MeCP2 expression status in the astrocytes and not in the neurons. Our findings highlight a new role for astrocytes in regulation of excitatory synaptic signaling and in the neurological defects associated with Rett syndrome.<\/jats:p>","DOI":"10.7554\/elife.31629","type":"journal-article","created":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T08:07:40Z","timestamp":1515485260000},"source":"Crossref","is-referenced-by-count":35,"title":["Astrocytic modulation of excitatory synaptic signaling in a mouse model of Rett syndrome"],"prefix":"10.7554","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4264-0562","authenticated-orcid":true,"given":"Benjamin","family":"Rakela","sequence":"first","affiliation":[{"name":"Vollum Institute, Oregon Health & Science University, Portland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Brehm","sequence":"additional","affiliation":[{"name":"Vollum Institute, Oregon Health & Science University, Portland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2085-4516","authenticated-orcid":true,"given":"Gail","family":"Mandel","sequence":"additional","affiliation":[{"name":"Vollum Institute, Oregon Health & Science University, Portland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2018,1,9]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S0079-6107(96)00013-2","article-title":"Gramicidin perforated patch recording and intracellular chloride activity in excitable cells","volume":"65","author":"Akaike","year":"1996","journal-title":"Progress in Biophysics and Molecular Biology"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1006\/nbdi.2001.0420","article-title":"Expression pattern of the Rett syndrome gene MeCP2 in primate prefrontal cortex","volume":"8","author":"Akbarian","year":"2001","journal-title":"Neurobiology of Disease"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/13810","article-title":"Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2","volume":"23","author":"Amir","year":"1999","journal-title":"Nature Genetics"},{"key":"bib4","doi-asserted-by":"crossref","first-page":"6822","DOI":"10.1523\/JNEUROSCI.18-17-06822.1998","article-title":"Calcium elevation in astrocytes causes an NMDA receptor-dependent increase in the frequency of miniature synaptic currents in cultured hippocampal neurons","volume":"18","author":"Araque","year":"1998","journal-title":"Journal of Neuroscience"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1002\/glia.10124","article-title":"Nitric oxide induces rapid, calcium-dependent release of vesicular glutamate and ATP from cultured rat astrocytes","volume":"40","author":"Bal-Price","year":"2002","journal-title":"Glia"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/nn.2275","article-title":"Non-cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology","volume":"12","author":"Ballas","year":"2009","journal-title":"Nature Neuroscience"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/nn.4201","article-title":"Astrocyte calcium signaling: the third wave","volume":"19","author":"Bazargani","year":"2016","journal-title":"Nature Neuroscience"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1113\/jphysiol.1989.sp017762","article-title":"Giant synaptic potentials in immature rat CA3 hippocampal neurones","volume":"416","author":"Ben-Ari","year":"1989","journal-title":"The Journal of Physiology"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1038\/nrn920","article-title":"Excitatory actions of gaba during development: the nature of the nurture","volume":"3","author":"Ben-Ari","year":"2002","journal-title":"Nature Reviews Neuroscience"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1113\/jphysiol.2010.203224","article-title":"Astrocytes control GABAergic inhibition of neurons in the mouse barrel cortex","volume":"589","author":"Benedetti","year":"2011","journal-title":"The Journal of Physiology"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1016\/j.neuron.2009.03.003","article-title":"Cation-chloride cotransporters and neuronal function","volume":"61","author":"Blaesse","year":"2009","journal-title":"Neuron"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.neuron.2007.10.001","article-title":"The story of Rett syndrome: from clinic to neurobiology","volume":"56","author":"Chahrour","year":"2007","journal-title":"Neuron"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1152\/jn.2000.84.1.428","article-title":"An excitatory GABAergic plexus in developing neocortical layer 1","volume":"84","author":"Dammerman","year":"2000","journal-title":"Journal of Neurophysiology"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1093\/hmg\/ddv464","article-title":"Altered microtubule dynamics and vesicular transport in mouse and human MeCP2-deficient astrocytes","volume":"25","author":"Del\u00e9pine","year":"2016","journal-title":"Human Molecular Genetics"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"e68851","DOI":"10.1371\/journal.pone.0068851","article-title":"Abnormal expression of cerebrospinal fluid cation chloride cotransporters in patients with Rett syndrome","volume":"8","author":"Duarte","year":"2013","journal-title":"PLoS One"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"6154080","DOI":"10.1155\/2016\/6154080","article-title":"Developmental dynamics of Rett syndrome","volume":"2016","author":"Feldman","year":"2016","journal-title":"Neural Plasticity"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/j.neuron.2004.08.011","article-title":"Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors","volume":"43","author":"Fellin","year":"2004","journal-title":"Neuron"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1523\/JNEUROSCI.2859-03.2004","article-title":"Intracellular astrocyte calcium waves in situ increase the frequency of spontaneous AMPA receptor currents in CA1 pyramidal neurons","volume":"24","author":"Fiacco","year":"2004","journal-title":"Journal of Neuroscience"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/S0092-8674(01)00341-5","article-title":"GABA itself promotes the developmental switch of neuronal GABAergic responses from excitation to inhibition","volume":"105","author":"Ganguly","year":"2001","journal-title":"Cell"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1152\/japplphysiol.00411.2015","article-title":"Conditional depletion of methyl-CpG-binding protein 2 in astrocytes depresses the hypercapnic ventilatory response in mice","volume":"119","author":"Garg","year":"2015","journal-title":"Journal of Applied Physiology"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1126\/science.1138389","article-title":"Reversal of neurological defects in a mouse model of Rett syndrome","volume":"315","author":"Guy","year":"2007","journal-title":"Science"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1038\/85899","article-title":"A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome","volume":"27","author":"Guy","year":"2001","journal-title":"Nature Genetics"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/1756-6606-4-32","article-title":"Activation of protease activated receptor 1 increases the excitability of the dentate granule neurons of hippocampus","volume":"4","author":"Han","year":"2011","journal-title":"Molecular Brain"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"9292","DOI":"10.1523\/JNEUROSCI.6063-08.2009","article-title":"Proteinase-activated receptors in the nucleus of the solitary tract: evidence for glial-neural interactions in autonomic control of the stomach","volume":"29","author":"Hermann","year":"2009","journal-title":"Journal of Neuroscience"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1139\/y97-110","article-title":"Proteinase-activated receptors: structural requirements for activity, receptor cross-reactivity, and receptor selectivity of receptor-activating peptides","volume":"75","author":"Hollenberg","year":"1997","journal-title":"Canadian Journal of Physiology and Pharmacology"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1038\/nm.3639","article-title":"GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease","volume":"20","author":"Jo","year":"2014","journal-title":"Nature Medicine"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/nn1849","article-title":"Glutamate exocytosis from astrocytes controls synaptic strength","volume":"10","author":"Jourdain","year":"2007","journal-title":"Nature Neuroscience"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1002\/neu.10201","article-title":"The expression of methyl CpG binding factor MeCP2 correlates with cellular differentiation in the developing rat brain and in cultured cells","volume":"55","author":"Jung","year":"2003","journal-title":"Journal of Neurobiology"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.expneurol.2004.02.018","article-title":"Protease-activated receptor-1 in human brain: localization and functional expression in astrocytes","volume":"188","author":"Junge","year":"2004","journal-title":"Experimental Neurology"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1038\/3684","article-title":"Astrocyte-mediated potentiation of inhibitory synaptic transmission","volume":"1","author":"Kang","year":"1998","journal-title":"Nature Neuroscience"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.mcn.2004.07.006","article-title":"MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions","volume":"27","author":"Kishi","year":"2004","journal-title":"Molecular and Cellular Neuroscience"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1002\/glia.10162","article-title":"Expression of voltage-gated Ca2+ channel subtypes in cultured astrocytes","volume":"41","author":"Latour","year":"2003","journal-title":"Glia"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1113\/jphysiol.2007.130377","article-title":"Astrocytic control of synaptic NMDA receptors","volume":"581","author":"Lee","year":"2007","journal-title":"The Journal of Physiology"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1002\/glia.21202","article-title":"Mechanisms of GABA release from human astrocytes","volume":"59","author":"Lee","year":"2011","journal-title":"Glia"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/nature10214","article-title":"A role for glia in the progression of Rett's syndrome","volume":"475","author":"Lioy","year":"2011","journal-title":"Nature"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"3172","DOI":"10.1073\/pnas.0306731101","article-title":"Astrocyte-mediated activation of neuronal kainate receptors","volume":"101","author":"Liu","year":"2004","journal-title":"PNAS"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"6033","DOI":"10.1073\/pnas.0401626101","article-title":"Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice","volume":"101","author":"Luikenhuis","year":"2004","journal-title":"PNAS"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1038\/nn.3434","article-title":"Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR\/SMRT co-repressor","volume":"16","author":"Lyst","year":"2013","journal-title":"Nature Neuroscience"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"5051","DOI":"10.1523\/JNEUROSCI.0324-09.2009","article-title":"Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions","volume":"29","author":"Maezawa","year":"2009","journal-title":"Journal of Neuroscience"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1126\/science.aaa7945","article-title":"Circuit-specific signaling in astrocyte-neuron networks in basal ganglia pathways","volume":"349","author":"Mart\u00edn","year":"2015","journal-title":"Science"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"e14199","DOI":"10.7554\/eLife.14199","article-title":"Manipulations of MeCP2 in glutamatergic neurons highlight their contributions to Rett and other neurological disorders","volume":"5","author":"Meng","year":"2016","journal-title":"eLife"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1038\/nn.3075","article-title":"Astrocyte signaling controls spike timing-dependent depression at neocortical synapses","volume":"15","author":"Min","year":"2012","journal-title":"Nature Neuroscience"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1126\/science.8134839","article-title":"Direct signaling from astrocytes to neurons in cultures of mammalian brain cells","volume":"263","author":"Nedergaard","year":"1994","journal-title":"Science"},{"key":"bib44","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1523\/JNEUROSCI.23-05-01659.2003","article-title":"Glial cell inhibition of neurons by release of ATP","volume":"23","author":"Newman","year":"2003","journal-title":"Journal of Neuroscience"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"10021","DOI":"10.1523\/JNEUROSCI.1316-12.2012","article-title":"MeCP2 is critical for maintaining mature neuronal networks and global brain anatomy during late stages of postnatal brain development and in the mature adult brain","volume":"32","author":"Nguyen","year":"2012","journal-title":"Journal of Neuroscience"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/0006-8993(78)90447-X","article-title":"Excitatory and inhibitory actions of GABA and glycine on embryonic chick spinal neurons in culture","volume":"144","author":"Obata","year":"1978","journal-title":"Brain Research"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"e35354","DOI":"10.1371\/journal.pone.0035354","article-title":"Alterations of gene expression and glutamate clearance in astrocytes derived from an MeCP2-null mouse model of Rett syndrome","volume":"7","author":"Okabe","year":"2012","journal-title":"PLoS One"},{"key":"bib48","doi-asserted-by":"crossref","first-page":"6414","DOI":"10.1523\/JNEUROSCI.16-20-06414.1996","article-title":"Excitatory GABA responses in embryonic and neonatal cortical slices demonstrated by gramicidin perforated-patch recordings and calcium imaging","volume":"16","author":"Owens","year":"1996","journal-title":"Journal of Neuroscience"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13041-015-0097-y","article-title":"Channel-mediated astrocytic glutamate modulates hippocampal synaptic plasticity by activating postsynaptic NMDA receptors","volume":"8","author":"Park","year":"2015","journal-title":"Molecular Brain"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1038\/369744a0","article-title":"Glutamate-mediated astrocyte-neuron signalling","volume":"369","author":"Parpura","year":"1994","journal-title":"Nature"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"2192","DOI":"10.1523\/JNEUROSCI.3965-04.2005","article-title":"Properties of synaptically evoked astrocyte calcium signal reveal synaptic information processing by astrocytes","volume":"25","author":"Perea","year":"2005","journal-title":"Journal of Neuroscience"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"2450","DOI":"10.1093\/cercor\/bhn009","article-title":"Astrocytes discriminate and selectively respond to the activity of a subpopulation of neurons within the barrel cortex","volume":"18","author":"Schipke","year":"2008","journal-title":"Cerebral Cortex"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/S0896-6273(02)00768-7","article-title":"Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3","volume":"35","author":"Shahbazian","year":"2002","journal-title":"Neuron"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"C524","DOI":"10.1152\/ajpcell.1996.271.2.C524","article-title":"Perforated patch-clamp recording in cardiac myocytes using cation-selective ionophore gramicidin","volume":"271","author":"Tajima","year":"1996","journal-title":"American Journal of Physiology-Cell Physiology"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1073\/pnas.1524013113","article-title":"KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome","volume":"113","author":"Tang","year":"2016","journal-title":"PNAS"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"3159","DOI":"10.1113\/JP270369","article-title":"Impaired CO2 sensitivity of astrocytes in a mouse model of Rett syndrome","volume":"593","author":"Turovsky","year":"2015","journal-title":"The Journal of Physiology"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1002\/(SICI)1098-1136(199712)21:4<361::AID-GLIA3>3.0.CO;2-6","article-title":"Characteristics of thrombin-induced calcium signals in rat astrocytes","volume":"21","author":"Ubl","year":"1997","journal-title":"Glia"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"e14198","DOI":"10.7554\/eLife.14198","article-title":"Restoration of Mecp2 expression in GABAergic neurons is sufficient to rescue multiple disease features in a mouse model of Rett syndrome","volume":"5","author":"Ure","year":"2016","journal-title":"eLife"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1523\/JNEUROSCI.3105-14.2015","article-title":"PAR1-activated astrocytes in the nucleus of the solitary tract stimulate adjacent neurons via NMDA receptors","volume":"35","author":"Vance","year":"2015","journal-title":"Journal of Neuroscience"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1152\/physrev.1998.78.1.99","article-title":"Glial calcium: homeostasis and signaling function","volume":"78","author":"Verkhratsky","year":"1998","journal-title":"Physiological Reviews"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"2968","DOI":"10.1093\/hmg\/ddu008","article-title":"Mutant astrocytes differentiated from Rett syndrome patients-specific iPSCs have adverse effects on wild-type neurons","volume":"23","author":"Williams","year":"2014","journal-title":"Human Molecular Genetics"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"15194","DOI":"10.1073\/pnas.2431073100","article-title":"Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine","volume":"100","author":"Yang","year":"2003","journal-title":"PNAS"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1016\/j.stemcr.2017.05.001","article-title":"Hypoxia epigenetically confers astrocytic differentiation potential on human pluripotent cell-derived neural precursor cells","volume":"8","author":"Yasui","year":"2017","journal-title":"Stem Cell Reports"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/nn980","article-title":"Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation","volume":"6","author":"Zonta","year":"2003","journal-title":"Nature Neuroscience"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/31629\/elife-31629-v3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/31629\/elife-31629-v3.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/31629","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:48:48Z","timestamp":1697057328000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/31629"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,9]]},"references-count":64,"alternative-id":["10.7554\/eLife.31629"],"URL":"https:\/\/doi.org\/10.7554\/elife.31629","archive":["CLOCKSS"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.732437997.793544041","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.31629.022","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.31629.021","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,9]]},"article-number":"e31629"}}