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The role of Akt in AMPA receptor insertion and LTP Yan, Yi


It has been widely accepted that long-term potentiation (LTP) in the hippocampal CA1 region mostly results from increased insertion of post-synaptic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs). The previous study in our lab has shown that activation of phosphatidylinositol 3-kinase (PI3K) by selective stimulation of synaptic N-methyl-D-aspartate receptors (NMDARs) is required for the increased cell surface expression of AMPARs and the consequent LTP. However, the following signaling pathways still remain unknown. In the present study, the involvement of Akt, the primary downstream protein kinase of PI3K, was examined with a combination of electrophysiological, biochemical and molecular biological techniques. The study found that Akt is required for the post-synaptic AMPAR insertion and LTP. Furthermore, the threonine 840 (Thr840) on GluRl C-tail was identified as a novel Akt phosphorylation site, suggesting a potential mechanism by which Akt contributes to AMPAR incorporation and LTP.

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