TY - JOUR
T1 - A role for the Ras signalling pathway in synaptic transmission and long- term memory
AU - Brambilla, Riccardo
AU - Gnesutta, Nerina
AU - Minichiello, Liliana
AU - White, Gail
AU - Roylance, Alistair J.
AU - Herron, Caroline E.
AU - Ramsey, Mark
AU - Wolfer, David P.
AU - Cestari, Vincenzo
AU - Rossi-Arnaud, Clelia
AU - Grant, Seth G N
AU - Chapman, Paul F.
AU - Lipp, Hans Peter
AU - Sturani, Emmapaola
AU - Klein, Rüdiger
PY - 1997/11/20
Y1 - 1997/11/20
N2 - 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.
AB - 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.
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M3 - Article
C2 - 9384379
AN - SCOPUS:0031581209
VL - 390
SP - 284
EP - 286
JO - Nature
JF - Nature
SN - 0028-0836
IS - 6657
ER -