Memories of MAP Kinase Activation

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Science  23 Oct 2009:
Vol. 326, Issue 5952, pp. 503
DOI: 10.1126/science.326_503c

We all know from experience that nothing beats repetition to help us store memories. New studies in the fruit fly of a gene associated with Noonan syndrome, which in humans causes abnormal development and learning disabilities, have implicated a role for signaling through the mitogen-activated protein kinase (MAPK) pathway in the consolidation of long-term memories in the brain. Mutations that cause Noonan syndrome are clustered in components of the MAPK signaling pathway, in particular, the gene encoding the protein tyrosine phosphatase PTPN11. Pagani et al. characterized the effects of the Drosophila ortholog of PTPN11, called corkscrew (CSW), that promotes MAPK signaling. In a learning task in which repetition of exposure to a stimulus was required to produce long-term memory and in which the time between training events was also critical, genetic or pharmacological inhibition of CSW specifically inhibited long-term memory formation. Overexpression of CSW in brain neurons altered the intervals required between trials. Successful generation of long-term memories was correlated with conditions that allowed a transient peak in MAPK activity after each training trial. Thus, waves of MAPK signaling may be part of the molecular mechanism through which properly spaced repetitions of a task produce long-term memories.

Cell 139, 186 (2009).

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