PI3 kinase signaling is required for retrieval and extinction of contextual memory.
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.
Chen
Xi
X
Department of Pharmacology, University of Washington, Box 357280, Seattle, Washington 98195-7280, USA.
Garelick
Michael G
MG
Wang
Hongbing
H
Lil
Vicky
V
Athos
Jaime
J
Storm
Daniel R
DR
D000818:Animals; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005108:Extinction, Psychological / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology; D011939:Mental Recall / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*
D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases