PI3 kinase signaling is required for retrieval and extinction of contextual memory

Nat Neurosci. 2005 Jul;8(7):925-31. doi: 10.1038/nn1482.


Memory retrieval is a dynamic aspect of memory formation that can be studied separately from other stages of memory processing. Although several signal transduction pathways including ERK/MAP kinase have been implicated in memory retrieval, the underlying signaling events are poorly defined. Here we report that re-exposure of mice to context after contextual training stimulates the activity of phosphatidylinositol 3 kinase (PI3K) in the hippocampus. Inhibition of PI3K activity in the hippocampus in vivo blocked contextual memory retrieval and extinction. Inhibitors of PI3K signaling also blocked increases in ERK/MAP kinase activity associated with memory retrieval. This suggests that PI3K activation in the hippocampus is critical for memory retrieval and is required for activation of ERK/MAP kinase during retrieval.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Chromones / pharmacology
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Enzyme Inhibitors / pharmacology
  • Extinction, Psychological / physiology*
  • Male
  • Memory / physiology
  • Mental Recall / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • Morpholines / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / physiology*


  • Chromones
  • Enzyme Inhibitors
  • Morpholines
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinases