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Here, we report that disrupted signaling mediated <jats:styled-content style=\"fixed-case\">MET<\/jats:styled-content> receptor tyrosine kinase (<jats:styled-content style=\"fixed-case\">RTK<\/jats:styled-content>), an established risk factor for autism spectrum disorders, in the developing hippocampus glutamatergic circuit leads to profound deficits in neural development, synaptic transmission, and plasticity. In cultured hippocampus slices prepared from neonatal mice, pharmacological inhibition of <jats:styled-content style=\"fixed-case\">MET<\/jats:styled-content> kinase activity suppresses dendritic arborization and disrupts normal dendritic spine development. In addition, single\u2010neuron knockdown (<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>i) or overexpression of <jats:italic>Met<\/jats:italic> in the developing hippocampal <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>1 neurons leads to alterations, opposite in nature, in basal synaptic transmission and long\u2010term plasticity. In forebrain\u2010specific <jats:italic>Met<\/jats:italic> conditional knockout mice (<jats:italic>Met<\/jats:italic><jats:sup>fx\/fx<\/jats:sup>;<jats:italic>emx1<\/jats:italic><jats:sup>cre<\/jats:sup>), an enhanced long\u2010term potentiation (<jats:styled-content style=\"fixed-case\">LTP<\/jats:styled-content>) and long\u2010term depression (<jats:styled-content style=\"fixed-case\">LTD<\/jats:styled-content>) were observed at early developmental stages (P12\u201314) at the Schaffer collateral to <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>1 synapses compared with wild\u2010type littermates. In contrast, <jats:styled-content style=\"fixed-case\">LTP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">LTD<\/jats:styled-content> were markedly reduced at young adult stage (P56\u201370) during which wild\u2010type mice show robust <jats:styled-content style=\"fixed-case\">LTP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">LTD<\/jats:styled-content>. The altered trajectory of synaptic plasticity revealed by this study indicate that temporally regulated <jats:styled-content style=\"fixed-case\">MET<\/jats:styled-content> signaling as an intrinsic, cell autonomous, and pleiotropic mechanism not only critical for neuronal growth and functional maturation, but also for the timing of synaptic plasticity during forebrain glutamatergic circuits development.<\/jats:p>","DOI":"10.1002\/dneu.22645","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T19:28:55Z","timestamp":1539199735000},"page":"36-50","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Disruption of <scp>MET<\/scp> Receptor Tyrosine Kinase, an Autism Risk Factor, Impairs Developmental Synaptic Plasticity in the Hippocampus"],"prefix":"10.1002","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7900-6779","authenticated-orcid":false,"given":"Xiaokuang","family":"Ma","sequence":"first","affiliation":[{"name":"Basic Medical Sciences University of Arizona College of Medicine\u2010Phoenix Phoenix Arizona 85004"},{"name":"Department of Pharmacology Shantou University Medical College Shantou Guangdong 515041 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Chen","sequence":"additional","affiliation":[{"name":"Basic Medical Sciences University of Arizona College of Medicine\u2010Phoenix Phoenix Arizona 85004"},{"name":"MOE Key Laboratory for NeuroInformation, The Clinical Hospital of Chengdu Brain Sciences Institute University of Electronic Science and Technology of China Chengdu Sichuan 610054 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongming","family":"Lu","sequence":"additional","affiliation":[{"name":"Basic Medical Sciences University of Arizona College of Medicine\u2010Phoenix Phoenix Arizona 85004"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariel","family":"Piechowicz","sequence":"additional","affiliation":[{"name":"Basic Medical Sciences University of Arizona College of Medicine\u2010Phoenix Phoenix Arizona 85004"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Barrow Neurological Institute St. Joseph's Hospital Medical Center Phoenix Arizona 85013"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"Basic Medical Sciences University of Arizona College of Medicine\u2010Phoenix Phoenix Arizona 85004"},{"name":"Barrow Neurological Institute St. Joseph's Hospital Medical Center Phoenix Arizona 85013"},{"name":"Department of Pharmacology Shantou University Medical College Shantou Guangdong 515041 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0730-1602","authenticated-orcid":false,"given":"Shenfeng","family":"Qiu","sequence":"additional","affiliation":[{"name":"Basic Medical Sciences University of Arizona College of Medicine\u2010Phoenix Phoenix Arizona 85004"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,21]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.06.031"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1153"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(91)90084-V"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2012-13-7-247"},{"issue":"3","key":"e_1_2_5_6_1","first-page":"1","article-title":"Autism as the early closure of a neuroplastic critical period normally seen in adolescence","volume":"2","author":"Berger 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