Fear memory formation involves p190 RhoGAP and ROCK proteins through a GRB2-mediated complex
Fear memory formation involves p190 RhoGAP and ROCK proteins through a GRB2-mediated complex
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DOI：
10.1016/s0896-6273(02)01047-4
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发表时间：
2002-11-14
期刊：
影响因子：
16.2
通讯作者：
LeDoux, JE
中科院分区：
文献类型：
--
作者：
Lamprecht, R;Farb, CR;LeDoux, JE
我们使用恐惧条件反射来研究长期记忆的分子机制，恐惧条件反射可以改变外侧杏仁核（LA）的突触功效。在恐惧条件反射后，LA 中酪氨酸磷酸化蛋白 p190 RhoGAP 与 GRB2 的相关性在条件反射大鼠中显着高于对照大鼠。还发现在条件反射动物中，RasGAP 和 Shc 与 LA 中的 GRB2 的关联显着更多。在恐惧调节过程中，LA 中 p190 RhoGAP 下游激酶 ROCK 的抑制会损害长期记忆，但不会损害短期记忆。因此，p190 RhoGAP/ROCK 通路在神经发育过程中调节树突和轴突的形态，通过 GRB2 介导的分子复合物，在外侧杏仁核的恐惧记忆形成中发挥着核心作用。
We used fear conditioning, which is known to alter synaptic efficacy in lateral amygdala (LA), to study molecular mechanisms underlying long-term memory. Following fear conditioning, the tyrosine phosphorylated protein p190 RhoGAP becomes associated with GRB2 in LA significantly more in conditioned than in control rats. RasGAP and Shc were also found to associate with GRB2 in LA significantly more in the conditioned animals. Inhibition of the p190 RhoGAP-downstream kinase ROCK in LA during fear conditioning impaired long- but not short-term memory. Thus, the p190 RhoGAP/ROCK pathway, which regulates the morphology of dendrites and axons during neural development, plays a central role, through a GRB2-mediated molecular complex, in fear memory formation in the lateral amygdala.