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LIMK, Cofilin 1 and actin dynamics involvement in fear memory processing.
Neurobiology of Learning and Memory ( IF 2.7 ) Pub Date : 2020-07-11 , DOI: 10.1016/j.nlm.2020.107275
Candela Medina 1 , Verónica de la Fuente 1 , Susanne Tom Dieck 2 , Belquis Nassim-Assir 2 , Tamas Dalmay 2 , Ina Bartnik 2 , Paula Lunardi 3 , Lucas de Oliveira Alvares 3 , Erin M Schuman 2 , Johannes J Letzkus 2 , Arturo Romano 1
Affiliation  

Long-term memory has been associated with morphological changes in the brain, which in turn tightly correlate with changes in synaptic efficacy. Such plasticity is proposed to rely on dendritic spines as a neuronal canvas on which these changes can occur. Given the key role of actin cytoskeleton dynamics in spine morphology, major regulating factors of this process such as Cofilin 1 (Cfl1) and LIM kinase (LIMK), an inhibitor of Cfl1 activity, are prime molecular targets that may regulate dendritic plasticity. Using a contextual fear conditioning paradigm in mice, we found that pharmacological induction of depolymerization of actin filaments through the inhibition of LIMK causes an impairment in memory reconsolidation, as well as in memory consolidation. On top of that, Cfl1 activity is inhibited and its mRNA is downregulated in CA1 neuropil after re-exposure to the training context. Moreover, by pharmacological disruption of actin cytoskeleton dynamics, the process of memory extinction can either be facilitated or impaired. Our results lead to a better understanding of the role of LIMK, Cfl1 and actin cytoskeleton dynamics in the morphological and functional changes underlying the synaptic plasticity of the memory trace.



中文翻译:

LIMK,Cofilin 1和肌动蛋白动力学参与恐惧记忆处理。

长期记忆与大脑的形态变化有关,而形态变化又与突触功效的变化紧密相关。提出这种可塑性依赖于树突棘作为神经元画布,这些变化可在其上发生。鉴于肌动蛋白细胞骨架动力学在脊柱形态中的关键作用,该过程的主要调节因子,如Cofilin 1(Cfl1​​)和LIM激酶(LIMK)(Cfl1​​活性的抑制剂),是可能调节树突状可塑性的主要分子靶标。在小鼠中使用上下文恐惧条件范式,我们发现通过抑制LIMK的药理作用诱导肌动蛋白丝解聚会导致记忆重建以及记忆巩固的损害。最重要的是,重新暴露于训练环境后,CA1 Neuropil中的Cfl1活性受到抑制,其mRNA下调。此外,通过肌动蛋白细胞骨架动力学的药理学破坏,可以促进或削弱记忆消失的过程。我们的结果导致对LIMK,Cfl1和肌动蛋白细胞骨架动力学在记忆轨迹的突触可塑性基础的形态和功能变化中的作用有了更好的了解。

更新日期:2020-07-25
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