Activation of P13-kinase is required for AMPA receptor insertion during LTP of mEPSCs in cultured hippocampal neurons

作者：Man HY; Wang QH; Lu WY; Ju W; Ahmadian G; Liu LD; D'Souza S; Wong TP; Taghibiglou C; Lu J; Becker LE; Pei L; Liu F; Wymann MP; MacDonald JF; Wang YT^*

来源：Neuron, 2003, 38(4): 611-624.

DOI：10.1016/S0896-6273(03)00228-9

Hippocampal CA1 homosynaptic long-term potentiation (LTP) is expressed specifically at activated synapses. Increased insertion of postsynaptic alpha-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.

• 出版日期2003-5-22