A role for the Ras signalling pathway in synaptic transmission and long- term memory

Riccardo Brambilla, Nerina Gnesutta, Liliana Minichiello, Gail White, Alistair J. Roylance, Caroline E. Herron, Mark Ramsey, David P. Wolfer, Vincenzo Cestari, Clelia Rossi-Arnaud, Seth G N Grant, Paul F. Chapman, Hans Peter Lipp, Emmapaola Sturani, Rüdiger Klein

Research output: Contribution to journalArticlepeer-review


Members of the Ras subfamily of small guanine-nucleotide-binding proteins are essential for controlling normal and malignant cell proliferation as well as cell differentiation. The neuronal-specific guanine- nucleotide-exchange factor, Ras-GRF/CDC25Mm (refs 24), induces Ras signalling in response to Ca2+ influx and activation of G-protein-coupled receptors in vitro, suggesting that it plays a role in neurotransmission and plasticity in vivo. Here we report that mice lacking Ras-GRF are impaired in the process of memory consolidation, as revealed by emotional conditioning tasks that require the function of the amygdala; learning and short-term memory are intact. Electrophysiological measurements in the basolateral amygdala reveal that long-term plasticity is abnormal in mutant mice. In contrast, Ras-GRF mutants do not reveal major deficits in spatial learning tasks such as the Morris water maze, a test that requires hippocampal function. Consistent with apparently normal hippocampal functions, Ras-GRF mutants show normal NMDA (N- methyl-D-aspartate) receptor-dependent long-term potentiation in this structure. These results implicate Ras-GRF signalling via the Ras/MAP kinase pathway in synaptic events leading to formation of long-term memories.

Original languageEnglish
Pages (from-to)284-286
Number of pages3
Issue number6657
Publication statusPublished - Nov 20 1997

ASJC Scopus subject areas

  • General


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