文章基本信息

标题：Sustained postsynaptic kainate receptor activation downregulates AMPA receptor surface expression and induces hippocampal LTD
本地全文：下载
作者：Jithin D. Nair ; Ellen Braksator ; Busra P. Yucel 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：9
页码：1-21
DOI：10.1016/j.isci.2021.103029
语种：English
出版社：Elsevier
摘要：SummaryIt is well established that long-term depression (LTD) can be initiated by either NMDA or mGluR activation. Here we report that sustained activation of GluK2 subunit-containing kainate receptors (KARs) leads to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) endocytosis and induces LTD of AMPARs (KAR-LTDAMPAR) in hippocampal neurons. The KAR-evoked loss of surface AMPARs is blocked by the ionotropic KAR inhibitor UBP 310 indicating that KAR-LTDAMPARrequires KAR channel activity. Interestingly, however, blockade of PKC or PKA also reduces GluA2 surface expression and occludes the effect of KAR activation. In acute hippocampal slices, kainate application caused a significant loss of GluA2-containing AMPARs from synapses and long-lasting depression of AMPAR excitatory postsynaptic currents in CA1. These data, together with our previously reported KAR-LTPAMPAR, demonstrate that KARs can bidirectionally regulate synaptic AMPARs and synaptic plasticity via different signaling pathways.Graphical abstractDisplay OmittedHighlights•Sustained kainate receptor (KAR) activation downregulates surface AMPARs•KAR ionotropic signaling induces AMPAR LTD (KAR-LTDAMPAR)•KAR-LTDAMPARis dependent on the GluK2 KAR subunit and calcineurinMolecular neuroscience; Cellular neuroscience