A role for hippocampal Rho-ROCK pathway in long-term spatial memory

A role for hippocampal Rho-ROCK pathway in long-term spatial memory
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DOI:
10.1016/j.bbrc.2004.08.004
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发表时间:
2004-09-24
影响因子:
3.1
通讯作者:
Moore, AN
Moore, AN
中科院分区:
生物学4区
文献类型:
--
作者:
Dash, PK;Orsi, SA;Moore, AN

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在许多物种中都观察到神经元的形态变化,包括突触大小、形状和数量的变化,并且被认为对于长期记忆存储至关重要。肌动蛋白丝与神经元形态密切相关,对其动态的调节可以影响记忆。 Rho GTPase 在此过程中发挥着重要作用,并且与突触前和突触后的形态变化有关。因此,我们研究了海马操纵 Rho 和 ROCK 活动对空间记忆任务表现的影响。训练后海马内注射下游效应激酶 p160ROCK 抑制剂会损害长期记忆。此外,训练后使用溶血磷脂酸 (LPA) 激活 Rho 可以增强长期空间记忆。 LPA 的这种记忆增强作用不是通过 Erk 级联介导的,因为没有观察到服用 LPA 后 Erk 磷酸化发生变化。我们的结果证明了 Rho-ROCK 通路在海马依赖性空间记忆中的作用。 (C) 2004 Elsevier Inc. 保留所有权利。
Morphological changes, including changes in size, shape, and number of synapses, in neurons have been observed in many species and are thought to be critical for long-term memory storage. Actin filaments are intimately involved in neuronal morphology and regulation of their dynamics can influence memory. Rho GTPase plays a prominent role in this process and has been implicated in both pre- and post-synaptic morphological changes. Therefore, we examined the effect of hippocampal manipulation of Rho and ROCK activity on performance in a spatial memory task. Post-training intrahippocampal infusion of an inhibitor of the downstream effector kinase p160ROCK impaired long-term memory. Furthermore, post-training activation of Rho using lysophosphatidic acid (LPA) enhanced long-term spatial memory. This memory enhancing effect of LPA was not mediated via the Erk cascade, as no change in Erk phosphorylation was observed as a result of its administration. Our results demonstrate a role for the Rho-ROCK pathway in hippocampus-dependent spatial memory. (C) 2004 Elsevier Inc. All rights reserved.