Sustained postsynaptic kainate receptor activation downregulates AMPA receptor surface expression and induces hippocampal LTD.

ABSTRACT: It 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-LTD_AMPAR) in hippocampal neurons. The KAR-evoked loss of surface AMPARs is blocked by the ionotropic KAR inhibitor UBP 310 indicating that KAR-LTD_AMPAR requires 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

SUBMITTER: Nair JD 

PROVIDER: S-EPMC8441151 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature