Neuron
Volume 36, Issue 3, 24 October 2002, Pages 493-505
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Article
Inhibitory Autophosphorylation of CaMKII Controls PSD Association, Plasticity, and Learning

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Abstract

To investigate the function of the α calcium-calmodulin-dependent kinase II (αCaMKII) inhibitory autophosphorylation at threonines 305 and/or 306, we generated knockin mice that express αCaMKII that cannot undergo inhibitory phosphorylation. In addition, we generated mice that express the inhibited form of αCaMKII, which resembles the persistently phosphorylated kinase at these sites. Our data demonstrate that blocking inhibitory phosphorylation increases CaMKII in the postsynaptic density (PSD), lowers the threshold for hippocampal long-term potentiation (LTP), and results in hippocampal-dependent learning that seems more rigid and less fine-tuned. Mimicking inhibitory phosphorylation dramatically decreased the association of CaMKII with the PSD and blocked both LTP and learning. These data demonstrate that inhibitory phosphorylation has a critical role in plasticity and learning.

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Present address: Memory Pharmaceuticals Corp., 100 Philips Parkway, Montvale, New Jersey 07645.

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Present address: Wolfson Institute for Biomedical Research, University College London, Gower Street, WC1E 6BT London, United Kingdom.