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

Neuron. 2003 May 22;38(4):611-24. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Cells, Cultured
  • Chromones / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / cytology*
  • Long-Term Potentiation / physiology*
  • Mice
  • Morpholines / pharmacology
  • Neuronal Plasticity / physiology
  • Neurons / cytology
  • Neurons / physiology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Transport / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism*
  • Signal Transduction / physiology
  • Wortmannin


  • Androstadienes
  • Chromones
  • Enzyme Inhibitors
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptors, AMPA
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Wortmannin