{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:28:56Z","timestamp":1784719736339,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2017,7,12]],"date-time":"2017-07-12T00:00:00Z","timestamp":1499817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS\u2010065027"],"award-info":[{"award-number":["NS\u2010065027"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001819","name":"International Rett Syndrome Foundation","doi-asserted-by":"publisher","award":["IRSF\u20103177"],"award-info":[{"award-number":["IRSF\u20103177"]}],"id":[{"id":"10.13039\/100001819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,8,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Rett syndrome is a neurodevelopmental disorder caused by loss\u2010of\u2010function mutations in <jats:italic>MECP2<\/jats:italic>, the gene encoding the transcriptional regulator methyl\u2010CpG\u2010binding protein 2 (MeCP2). <jats:italic>Mecp2<\/jats:italic> deletion in mice results in an imbalance of excitation and inhibition in hippocampal neurons, which affects \u2018Hebbian\u2019 synaptic plasticity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We show that <jats:italic>Mecp2<\/jats:italic>\u2010deficient neurons also lack homeostatic synaptic plasticity, likely due to reduced levels of EEA1, a protein involved in AMPA receptor endocytosis.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Expression of EEA1 restored homeostatic synaptic plasticity in <jats:italic>Mecp2<\/jats:italic>\u2010deficient neurons, providing novel targets of intervention in Rett syndrome.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Rett syndrome is a neurodevelopmental disorder caused by loss\u2010of\u2010function mutations in <jats:italic>MECP2<\/jats:italic>, the gene encoding the transcriptional regulator methyl\u2010CpG\u2010binding protein 2 (MeCP2). Deletion of <jats:italic>Mecp2<\/jats:italic> in mice results in an imbalance of synaptic excitation and inhibition in hippocampal pyramidal neurons, which affects \u2018Hebbian\u2019 long\u2010term synaptic plasticity. Since the excitatory\u2013inhibitory balance is maintained by homeostatic mechanisms, we examined the role of MeCP2 in homeostatic synaptic plasticity (HSP) at excitatory synapses. Negative feedback HSP, also known as synaptic scaling, maintains the global synaptic strength of individual neurons in response to sustained alterations in neuronal activity. Hippocampal neurons from <jats:italic>Mecp2<\/jats:italic> knockout (KO) mice do not show the characteristic homeostatic scaling up of the amplitude of miniature excitatory postsynaptic currents (mEPSCs) and of synaptic levels of the GluA1 subunit of AMPA\u2010type glutamate receptors after 48\u00a0h silencing with the Na<jats:sup>+<\/jats:sup> channel blocker tetrodotoxin. This deficit in HSP is bidirectional because <jats:italic>Mecp2<\/jats:italic> KO neurons also failed to scale down mEPSC amplitudes and GluA1 synaptic levels after 48\u00a0h blockade of type A GABA receptor (GABA<jats:sub>A<\/jats:sub>R)\u2010mediated inhibition with bicuculline. Consistent with the role of synaptic trafficking of AMPA\u2010type of glutamate receptors in HSP, <jats:italic>Mecp2<\/jats:italic> KO neurons have lower levels of early endosome antigen 1 (EEA1), a protein involved in AMPA\u2010type glutamate receptor endocytosis. In addition, expression of EEA1 in <jats:italic>Mecp2<\/jats:italic> KO neurons reduced mEPSC amplitudes to wild\u2010type levels, and restored synaptic scaling down of mEPSC amplitudes after 48\u00a0h blockade of GABA<jats:sub>A<\/jats:sub>R\u2010mediated inhibition with bicuculline. The identification of a molecular deficit in HSP in <jats:italic>Mecp2<\/jats:italic> KO neurons provides potentially novel targets of intervention for improving hippocampal function in Rett syndrome individuals.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp274450","type":"journal-article","created":{"date-parts":[[2017,6,16]],"date-time":"2017-06-16T09:22:45Z","timestamp":1497604965000},"page":"5699-5712","source":"Crossref","is-referenced-by-count":35,"title":["EEA1 restores homeostatic synaptic plasticity in hippocampal neurons from Rett syndrome mice"],"prefix":"10.1113","volume":"595","author":[{"given":"Xin","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Civitan International Research Center University of Alabama at Birmingham  Birmingham AL 35294 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