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

Riccardo Brambilla, Nerina Gnesutta, Liliana Minichiello, Gail White, Alistair J. Roylance, Caroline E. Herron, Mark Ramsey, David P. Wolfer, Vincenzo Cestari, Clelia Rossi-Arnaud, Seth G N Grant, Paul F. Chapman, Hans Peter Lipp, Emmapaola Sturani, Rüdiger Klein

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)284-286
Number of pages3
JournalNature
Volume390
Issue number6657
Publication statusPublished - Nov 20 1997

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ras-GRF1
Long-Term Memory
Synaptic Transmission
Guanine Nucleotide Exchange Factors
Guanine Nucleotides
Long-Term Potentiation
G-Protein-Coupled Receptors
Amygdala
N-Methyl-D-Aspartate Receptors
Short-Term Memory
Cell Differentiation
Carrier Proteins
Phosphotransferases
Cell Proliferation
Learning
Water

ASJC Scopus subject areas

  • General

Cite this

Brambilla, R., Gnesutta, N., Minichiello, L., White, G., Roylance, A. J., Herron, C. E., ... Klein, R. (1997). A role for the Ras signalling pathway in synaptic transmission and long- term memory. Nature, 390(6657), 284-286.

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 journalArticle

Brambilla, R, Gnesutta, N, Minichiello, L, White, G, Roylance, AJ, Herron, CE, Ramsey, M, Wolfer, DP, Cestari, V, Rossi-Arnaud, C, Grant, SGN, Chapman, PF, Lipp, HP, Sturani, E & Klein, R 1997, 'A role for the Ras signalling pathway in synaptic transmission and long- term memory', Nature, vol. 390, no. 6657, pp. 284-286.
Brambilla R, Gnesutta N, Minichiello L, White G, Roylance AJ, Herron CE et al. A role for the Ras signalling pathway in synaptic transmission and long- term memory. Nature. 1997 Nov 20;390(6657):284-286.
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. / A role for the Ras signalling pathway in synaptic transmission and long- term memory. In: Nature. 1997 ; Vol. 390, No. 6657. pp. 284-286.
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