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The Journal of Neuroscience, June 1, 2002, 22(11):4406-4411

Multiple Mechanisms for the Potentiation of AMPA Receptor-Mediated Transmission by alpha -Ca2+/Calmodulin-Dependent Protein Kinase II

Jean Christophe Poncer1, 2, José A. Esteban1, and Roberto Malinow1

1 Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, and 2 Institut National de la Santé et de la Recherche Médicale, Cortex and Epilepsie, 75006 Paris, France

Some forms of activity-dependent synaptic potentiation require the activation of postsynaptic Ca2+/calmodulin-dependent protein kinase II (CaMKII). Activation of CaMKII has been shown to phosphorylate the glutamate receptor 1 subunit of the AMPA receptor (AMPAR), thereby affecting some of the properties of the receptor. Here, a recombinant, constitutively active form of alpha CaMKII tagged with the fluorescent marker green fluorescent protein (GFP) [alpha CaMKII1-290-enhanced GFP (EGFP)] was expressed in CA1 pyramidal neurons from hippocampal slices. The changes in glutamatergic transmission onto these cells were analyzed. AMPA but not NMDA receptor-mediated EPSCs were specifically potentiated in infected compared with nearby noninfected neurons. This potentiation was associated with a reduction in the proportion of synapses devoid of AMPARs. In addition, expression of alpha CaMKII1-290-EGFP increased the quantal size of AMPAR-mediated responses. This effect reflected, at least in part, an increased unitary conductance of the channels underlying the EPSCs. These results reveal that several key features of long-term potentiation of hippocampal glutamatergic synapses are reproduced by the sole activity of alpha CaMKII.

Key words: synaptic plasticity; CaMKII; viral transfection; silent synapses; AMPA receptors; LTP


Copyright © 2002 Society for Neuroscience  0270-6474/02/22114406-06$05.00/0


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