1. Activation of PI3-Kinase Is Required for AMPA Receptor Insertion during LTP of mEPSCs in Cultured Hippocampal Neurons
- Author
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Man, Heng-Ye, Wang, Qinhua, Lu, Wei-Yang, Ju, William, Ahmadian, Gholamreza, Liu, Lidong, D'Souza, Sandra, Wong, T.P., Taghibiglou, C., Lu, Jie, Becker, Larry E., Pei, Lin, Liu, Fang, Wymann, Matthias P., MacDonald, John F., and Wang, Yu Tian
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SYNAPSES , *NEUROLOGY - Abstract
Hippocampal CA1 homosynaptic long-term potentiation (LTP) is expressed specifically at activated synapses. Increased insertion of postsynaptic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs) appears to be crucial for CA1 LTP. However, the mechanism underlying AMPAR insertion during LTP remains largely unknown. We now report that phosphatidylinositol 3-kinase (PI3K) is complexed with AMPARs at synapses and activated by selective stimulation of synaptic N-methyl-D-aspartate (NMDA) receptors. Activation of the AMPAR-associated PI3K is required for the increased cell surface expression of AMPARs and LTP. Thus, our results strongly suggest that the AMPAR-PI3K complex may constitute a critical molecular signal responsible for AMPAR insertion at activated CA1 synapses during LTP, and consequently, this lipid kinase may serve to determine the polarity of NMDA receptor-dependent synaptic plasticity. [Copyright &y& Elsevier]
- Published
- 2003
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