Show simple item record

dc.contributor.authorMa, Xiaokuang
dc.contributor.authorChen, Ke
dc.contributor.authorLu, Zhongming
dc.contributor.authorPiechowicz, Mariel
dc.contributor.authorLiu, Qiang
dc.contributor.authorWu, Jie
dc.contributor.authorQiu, Shenfeng
dc.date.accessioned2019-05-08T17:24:27Z
dc.date.available2019-05-08T17:24:27Z
dc.date.issued2019-01-01
dc.identifier.citationMa, X. , Chen, K. , Lu, Z. , Piechowicz, M. , Liu, Q. , Wu, J. and Qiu, S. (2019), Disruption of MET Receptor Tyrosine Kinase, an Autism Risk Factor, Impairs Developmental Synaptic Plasticity in the Hippocampus. Develop Neurobiol, 79: 36-50. doi:10.1002/dneu.22645en_US
dc.identifier.issn1932-846X
dc.identifier.pmid30304576
dc.identifier.doi10.1002/dneu.22645
dc.identifier.urihttp://hdl.handle.net/10150/632212
dc.description.abstractAs more genes conferring risks to neurodevelopmental disorders are identified, translating these genetic risk factors into biological mechanisms that impact the trajectory of the developing brain is a critical next step. Here, we report that disrupted signaling mediated MET receptor tyrosine kinase (RTK), 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 MET kinase activity suppresses dendritic arborization and disrupts normal dendritic spine development. In addition, single-neuron knockdown (RNAi) or overexpression of Met in the developing hippocampal CA1 neurons leads to alterations, opposite in nature, in basal synaptic transmission and long-term plasticity. In forebrain-specific Met conditional knockout mice (Metfx/fx ;emx1cre ), an enhanced long-term potentiation (LTP) and long-term depression (LTD) were observed at early developmental stages (P12-14) at the Schaffer collateral to CA1 synapses compared with wild-type littermates. In contrast, LTP and LTD were markedly reduced at young adult stage (P56-70) during which wild-type mice show robust LTP and LTD. The altered trajectory of synaptic plasticity revealed by this study indicate that temporally regulated MET 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.en_US
dc.description.sponsorshipNational Institute of Mental Healthen_US
dc.language.isoenen_US
dc.publisherWILEYen_US
dc.relation.urlhttps://onlinelibrary.wiley.com/doi/full/10.1002/dneu.22645en_US
dc.rights© 2018 Wiley Periodicals, Inc.en_US
dc.subjectMET receptor tyrosine kinaseen_US
dc.subjectautismen_US
dc.subjecthippocampusen_US
dc.subjectneurodevelopmenten_US
dc.subjectsynaptic plasticityen_US
dc.titleDisruption of MET Receptor Tyrosine Kinase, an Autism Risk Factor, Impairs Developmental Synaptic Plasticity in the Hippocampusen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Coll Med Phoenix, Basic Med Scien_US
dc.identifier.journalDEVELOPMENTAL NEUROBIOLOGYen_US
dc.description.note12 month embargo; published online: 10 October 2018en_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal accepted manuscripten_US
dc.source.journaltitleDevelopmental neurobiology


Files in this item

Thumbnail
Name:
Ma_et_al_final_UA_library_open ...
Size:
1.497Mb
Format:
PDF
Description:
Final Accepted Manuscript

This item appears in the following Collection(s)

Show simple item record