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The use of hippocampal dissociated neuronal cultures has enabled the study of molecular changes in endogenous native proteins associated with long-term potentiation (LTP). Using immunofluorescence labelling of the active (Thr286-phosphorylated) alpha-Ca2+/calmodulin-dependent protein kinase II (CaMKII) we found that CaMKII activity was increased by transient (3x1 s) depolarisation in 18-21 day old cultures but not in 9-11 day old cultures. The increase in Thr286 phosphorylation of CaMKII required the activation of N-methyl-D-aspartate receptors (NMDARs) 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 (AMPAR) and found a preferential recruitment of the GluA1 subunit. CaMKII inhibition prevented this NMDAR-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 AMPARs to the cell surface of hippocampal neurons.
|Translated title of the contribution||LTP in hippocampal neurons is associated with a CaMKII-mediated increase in GluA1 surface expression|
|Pages (from-to)||530 - 543|
|Number of pages||14|
|Journal||Journal of Neurochemistry|
|Publication status||Published - Jan 2011|