Laboratório de Neurobiologia da Memória, Departamento de Biofísica, Instituto de Biociências, Universidade Federal do Rio Grande do Sul (UFRGS), Avenida Bento Gonçalves, 9500, Prédio 43422, Sala 216A, Porto Alegre, Rio Grande do Sul, 91501-970, Brazil.
Graduate Program in Neuroscience, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Mol Neurobiol. 2018 Feb;55(2):958-967. doi: 10.1007/s12035-016-0361-x. Epub 2017 Jan 13.
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.
树突棘的持久变化为记忆的形成和持久提供了物理相关物。LIM 激酶（LIMK）在记忆处理过程中协调树突状肌动蛋白动力学方面起着至关重要的作用，因为它是 Rac1/PAK 和 RhoA/ROCK 途径的收敛下游靶点，这反过来又诱导了丝切蛋白磷酸化并阻止了肌动蛋白丝的解聚。在这里，我们使用一种有效的 LIMK 抑制剂（BMS-5），研究了 LIMK 活性在大鼠情景恐惧记忆的背侧海马中的作用。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 也会破坏记忆的获取。然后，我们证明海马 LIMK 活性对于记忆检索和再巩固似乎是至关重要的，因为这两个过程都因 BMS-5 处理而受损。然而，情景恐惧记忆的消退对相同的处理并不敏感。总之，我们的发现表明，海马 LIMK 活性在情景恐惧条件作用期间的记忆获取、巩固、检索和再巩固中起着重要作用。
