Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK
Ellen Braksator
Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK
Busra P. Yucel
Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK
Alexandra Fletcher-Jones
Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK
Richard Seager
Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK
Jack R. Mellor
Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK
Zafar I. Bashir
Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK
Kevin A. Wilkinson
Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK; Corresponding author
Jeremy M. Henley
Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK; Centre for Neuroscience and Regenerative Medicine, Faculty of Science, University of Technology Sydney, Ultimo, NSW, Australia; Corresponding author
Summary: 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-LTDAMPAR) in hippocampal neurons. The KAR-evoked loss of surface AMPARs is blocked by the ionotropic KAR inhibitor UBP 310 indicating that KAR-LTDAMPAR 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 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.
