Abstract
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 language | English |
|---|---|
| Pages (from-to) | 284-286 |
| Number of pages | 3 |
| Journal | Nature |
| Volume | 390 |
| Issue number | 6657 |
| Publication status | Published - Nov 20 1997 |
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A role for the Ras signalling pathway in synaptic transmission and long- term memory. / Brambilla, Riccardo; Gnesutta, Nerina; Minichiello, Liliana; White, Gail; Roylance, Alistair J.; Herron, Caroline E.; Ramsey, Mark; Wolfer, David P.; Cestari, Vincenzo; Rossi-Arnaud, Clelia; Grant, Seth G N; Chapman, Paul F.; Lipp, Hans Peter; Sturani, Emmapaola; Klein, Rüdiger.
In: Nature, Vol. 390, No. 6657, 20.11.1997, p. 284-286.Research output: Contribution to journal › Article
}
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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UR - http://www.scopus.com/inward/citedby.url?scp=0031581209&partnerID=8YFLogxK
M3 - Article
C2 - 9384379
AN - SCOPUS:0031581209
VL - 390
SP - 284
EP - 286
JO - Nature
JF - Nature
SN - 0028-0836
IS - 6657
ER -