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.