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キーワード:
muscarinic receptors
exchange factor
protein
potentiation
activation
amygdala
mice
identification
plasticity
induction
Science & Technology - Other Topics
要旨:
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(1). The neuronal-specific guanine-nucleotide-exchange factor, Ras-GRF/CDC25Mm (refs 2-4), induces Ras signalling in response to Ca2+ influx(5) and activation of G-protein-coupled receptors in vitro(6), suggesting that it plays a role in neurotransmission and plasticity in vivo(7). 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.
