A role for the PI-3 kinase signaling pathway in fear conditioning and synaptic plasticity in the amygdala

被引:294
作者
Lin, CH [1 ]
Yeh, SH [1 ]
Lin, CH [1 ]
Lu, KT [1 ]
Leu, TH [1 ]
Chang, WC [1 ]
Gean, PW [1 ]
机构
[1] Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 70101, Taiwan
关键词
D O I
10.1016/S0896-6273(01)00433-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Western blot analysis of neuronal tissues taken from fear-conditioned rats showed a selective activation of phosphatidylinositol 3-kinase (PI-3 kinase) in the amygdala. PI-3 kinase was also activated in response to long-term potentiation (LTP)-inducing tetanic stimulation. PI-3 kinase inhibitors blocked tetanus-induced LTP as well as PI-3 kinase activation. In parallel, these inhibitors interfered with long-term fear memory while leaving short-term memory intact. Tetanus and forskolin-induced activation of mitogen-activated protein kinase (MAPK) was blocked by PI-3 kinase inhibitors, which also inhibited cAMP response element binding protein (CREB) phosphorylation. These results provide novel evidence of a requirement of PI-3 kinase activation in the amygdala for synaptic plasticity and memory consolidation, and this activation may occur at a point upstream of MAPK activation.
引用
收藏
页码:841 / 851
页数:11
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