[PDF][PDF] Activation of PI3-kinase is required for AMPA receptor insertion during LTP of mEPSCs in cultured hippocampal neurons

HY Man, Q Wang, WY Lu, W Ju, G Ahmadian, L Liu… - Neuron, 2003 - cell.com
HY Man, Q Wang, WY Lu, W Ju, G Ahmadian, L Liu, S D'Souza, TP Wong, C Taghibiglou
Neuron, 2003cell.com
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 …
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.
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