title: LTP in hippocampal neurons is associated with a CaMKII-mediated increase in GluA1 surface expression.
abstract: The use of hippocampal dissociated neuronal cultures has enabled the study of molecular changes in endogenous native proteins associated with long-term potentiation. Using immunofluorescence labelling of the active (Thr286-phosphorylated) alpha-Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) we found that CaMKII activity was increased by transient (3 × 1 s) depolarisation in 18- to 21-day-old cultures but not in 9- to 11-day-old cultures. The increase in Thr286 phosphorylation of CaMKII required the activation of NMDA receptors and was greatly attenuated by the CaMKII inhibitor KN-62. We compared the effects of transient depolarisation on the surface expression of GluA1 and GluA2 subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor and found a preferential recruitment of the GluA1 subunit. CaMKII inhibition prevented this NMDA receptor-dependent delivery of GluA1 to the cell surface. CaMKII activation is therefore an important factor in the activity-dependent recruitment of native GluA1 subunit-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors to the cell surface of hippocampal neurons.
authors.affiliation: MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
authors.forename: Vanessa J
authors.initials: VJ
authors.lastname: Appleby
authors.forename: Sonia A L
authors.initials: SA
authors.lastname: Corrêa
authors.forename: Joshua K
authors.initials: JK
authors.lastname: Duckworth
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Nash
authors.forename: Jacques
authors.initials: J
authors.lastname: Noël
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Fitzjohn
authors.forename: Graham L
authors.initials: GL
authors.lastname: Collingridge
authors.forename: Elek
authors.initials: E
authors.lastname: Molnár
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins / Q000096:biosynthesis; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D008565:Membrane Proteins; D018091:Receptors, AMPA; C063302:KN 62