A role for the Ras signalling pathway in synaptic transmission and long-term memory - PubMed (original) (raw)

. 1997 Nov 20;390(6657):281-6.

doi: 10.1038/36849.

N Gnesutta, L Minichiello, G White, A J Roylance, C E Herron, M Ramsey, D P Wolfer, V Cestari, C Rossi-Arnaud, S G Grant, P F Chapman, H P Lipp, E Sturani, R Klein

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

R Brambilla et al. Nature. 1997.

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, 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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