|Title||A role for the Ras signalling pathway in synaptic transmission and long-term memory.|
|Publication Type||Journal Article|
|Year of Publication||1997|
|Authors||Brambilla 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 Published||1997 Nov 20|
|Keywords||3T3 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.
|Grant List||/ / Wellcome Trust / United Kingdom|