Effects of Hippocampal LIMK Inhibition on Memory Acquisition, Consolidation, Retrieval, Reconsolidation, and Extinction
Effects of Hippocampal LIMK Inhibition on Memory Acquisition, Consolidation, Retrieval, Reconsolidation, and Extinction
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DOI：
10.1007/s12035-016-0361-x
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发表时间：
2018-02-01
影响因子：
5.1
通讯作者：
Alvares, Lucas de Oliveira
中科院分区：
文献类型：
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作者：
Lunardi, Paula;Sachser, Ricardo Marcelo;Alvares, Lucas de Oliveira
树突棘的长期变化为记忆的形成和持久性提供了物理相关性。LIM激酶（LIMK）在记忆处理过程中协调树突状肌动蛋白动力学中起着关键作用，因为它是Rac 1/PAK和RhoA/ROCK途径的会聚下游靶点，这反过来诱导cofilin磷酸化并防止肌动蛋白丝解聚。在这里，使用一种有效的LIMK抑制剂（BMS-5），我们研究了大鼠背景恐惧记忆过程中背海马LIMK活性的作用。我们首先发现，训练后给予BMS-5以剂量依赖性方式损害记忆巩固。在训练前抑制LIMK也会破坏记忆的获得。然后，我们证明了海马LIMK活性似乎对记忆恢复和再巩固至关重要，因为这两个过程都受到BMS-5治疗的损害。然而，情境性恐惧记忆消退对相同的治疗并不敏感。总之，我们的研究结果表明，海马LIMK活性起着重要的作用，在记忆的获得，巩固，检索和再巩固在上下文的恐惧条件。
Long-lasting changes in dendritic spines provide a physical correlate for memory formation and persistence. LIM kinase (LIMK) plays a critical role in orchestrating dendritic actin dynamics during memory processing, since it is the convergent downstream target of both the Rac1/PAK and RhoA/ROCK pathways that in turn induce cofilin phosphorylation and prevent depolymerization of actin filaments. Here, using a potent LIMK inhibitor (BMS-5), we investigated the role of LIMK activity in the dorsal hippocampus during contextual fear memory in rats. We first found that post-training administration of BMS-5 impaired memory consolidation in a dose-dependent manner. Inhibiting LIMK before training also disrupted memory acquisition. We then demonstrated that hippocampal LIMK activity seems to be critical for memory retrieval and reconsolidation, since both processes were impaired by BMS-5 treatment. Contextual fear memory extinction, however, was not sensitive to the same treatment. In conclusion, our findings demonstrate that hippocampal LIMK activity plays an important role in memory acquisition, consolidation, retrieval, and reconsolidation during contextual fear conditioning.