Pharmacological inactivation of the small GTPase Rac1 impairs long-term plasticity in the mouse hippocampus.
Pharmacological inactivation of the small GTPase Rac1 impairs long-term plasticity in the mouse hippocampus.
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DOI：
10.1016/j.neuropharm.2011.04.017
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发表时间：
2011-07
影响因子：
4.7
通讯作者：
Tejada-Simon MV
中科院分区：
文献类型：
--
作者：
Martinez LA;Tejada-Simon MV
神经元发育包括几个离散的形态学步骤，需要新生神经元迁移到特征位置，轴突和树突延伸到适当的目标区域，以及与合适的伙伴形成突触。小的gtp酶，如Rac1，被认为是这些过程的关键调节者。我们之前报道过Rac1在小鼠海马中高表达，其中NMDA受体激活导致Rac1以与其他非神经元细胞相似的方式转移到膜上。此外，Rac1已被发现在激活与海马学习和记忆相关的信号转导通路中发挥作用。由于LTP和LTD在学习和记忆过程中的作用已经确立，在本研究中，我们研究了Rac1是否在这些类型的长期突触可塑性中也起着积极和关键的作用。我们发现Rac1的激活与LTP和LTD的长期可塑性有关。在NMDA受体依赖性LTP的诱导过程中，Rac1似乎具有短暂的作用，但对LTP的维持和表达没有影响。NMDA受体依赖性诱导LTD的结果类似，而mglur依赖性LTD被证明显著改变但未被消除。这些实验的结果提供了关于突触可塑性的信号机制以及学习和记忆过程的基本知识，这反过来又为涉及记忆障碍的疾病的基础提供了见解，如脆性X综合征、阿尔茨海默病、威廉综合征、安吉尔曼综合征（as）和精神分裂症。
Neuronal development involves several discrete morphological steps requiring migration of newborn neurons to characteristic locations, extension of axons and dendrites into proper target regions, and formation of synapses with appropriate partners. Small GTPases such as Rac1, are believed to be critical regulators of these processes. We have previously reported that Rac1 is highly expressed in mouse hippocampus, where NMDA receptor activation causes Rac1 to translocate to the membrane in a manner similar to that observed in other non-neuronal cells. Additionally Rac1 has been seen to play a role in activation of signal transduction pathways associated with hippocampal learning and memory. Because of the established role of LTP and LTD in learning and memory processes, in this study we investigate whether Rac1 plays also an active and critical role in these types of long-term synaptic plasticity. We found that activation of Rac1 is associated with long-term plasticity, both LTP and LTD. Rac1 appears to have a transient role during the induction of NMDA receptor-dependent LTP, but does not have an effect on LTP maintenance and expression. Similar results were found for NMDA receptor-dependent induction of LTD, while mGluR-dependent LTD was shown to be significantly altered but not abolished. The results of these experiments provide essential knowledge regarding the signaling mechanisms that underlie synaptic plasticity, as well as learning and memory processes, which in turn offers insights into the basis of diseases involving memory impairment, such as Fragile X syndrome, Alzheimer’s disease, William’s syndrome, Angelman syndrome (AS), and schizophrenia.
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DOI：
10.1073/pnas.0610059104
发表时间：
2007-01-09
影响因子：
11.1
作者：
Diana, Giovanni;Valentini, Giovanni;Fiorentini, Carla
通讯作者：
Fiorentini, Carla
影响因子：
3.4
作者：
Nakao, K;Ikegaya, Y;Matsuki, N
通讯作者：
Matsuki, N
影响因子：
3.4
作者：
Naie, K;Manahan-Vaughan, D
通讯作者：
Manahan-Vaughan, D
影响因子：
56.9
作者：
PURPURA, DP
通讯作者：
PURPURA, DP
影响因子：
5.5
作者：
COLLINGRIDGE, GL;KEHL, SJ;MCLENNAN, H
通讯作者：
MCLENNAN, H