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

Autor: Nair JD; Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK., Braksator E; Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK., Yucel BP; Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK., Fletcher-Jones A; Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK., Seager R; Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK., Mellor JR; 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., Bashir ZI; 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., Wilkinson KA; Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK., Henley JM; 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.
Jazyk: angličtina
Zdroj: IScience [iScience] 2021 Aug 25; Vol. 24 (9), pp. 103029. Date of Electronic Publication: 2021 Aug 25 (Print Publication: 2021).
DOI: 10.1016/j.isci.2021.103029
Abstrakt: 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 of AMPAR excitatory postsynaptic currents in CA1. These data, together with our previously reported KAR-LTP AMPAR , demonstrate that KARs can bidirectionally regulate synaptic AMPARs and synaptic plasticity via different signaling pathways.
Competing Interests: The authors declare no competing interests.
(© 2021 The Authors.)
Databáze: MEDLINE
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