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

TitleA role for the Ras signalling pathway in synaptic transmission and long-term memory.
Publication TypeJournal Article
Year of Publication1997
AuthorsBrambilla R, Gnesutta N, Minichiello L, White G, Roylance AJ, Herron CE, Ramsey M, Wolfer DP, Cestari V, Rossi-Arnaud C, Grant SG, Chapman PF, Lipp HP, Sturani E, Klein R
Date Published1997 Nov 20
Keywords3T3 Cells, Amygdala, Animals, Avoidance Learning, Brain, Cell Cycle Proteins, Conditioning, Classical, Electrophysiology, Fear, Hippocampus, Maze Learning, Memory, Mice, Mice, Inbred C57BL, Mutagenesis, Neuronal Plasticity, Phosphoprotein Phosphatases, ras Proteins, ras-GRF1, Signal Transduction, Spatial Behavior, Synapses

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, 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.

Alternate JournalNature
PubMed ID9384379
Grant List / / Wellcome Trust / United Kingdom