Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, People's Republic of China.
J Neurosci. 2013 Apr 10;33(15):6423-33. doi: 10.1523/JNEUROSCI.5107-12.2013.
Actin dynamics provide an important mechanism for the modification of synaptic plasticity, which is regulated by the actin depolymerizing factor (ADF)/cofilin. However, the role of cofilin regulated actin dynamics in memory extinction process is still unclear. Here, we observed that extinction of conditioned taste aversive (CTA) memory led to temporally enhanced ADF/cofilin activity in the infralimbic cortex (IrL) of the rats. Moreover, temporally elevating ADF/cofilin activity in the IrL could accelerate CTA memory extinction by facilitating AMPAR synaptic surface recruitment, whereas inhibition of ADF/cofilin activity abolished AMPAR synaptic surface trafficking and impaired memory extinction. Finally, we observed that ADF/cofilin-regulated synaptic plasticity was not directly coupled to morphological changes of postsynaptic spines. These findings may help us understand the role of ADF/cofilin-regulated actin dynamics in memory extinction and suggest that appropriate manipulating ADF/cofilin activity might be a suitable way for therapeutic treatment of memory disorders.
肌动蛋白动力学为突触可塑性的修饰提供了一个重要的机制,而肌动蛋白解聚因子(ADF)/丝切蛋白对此进行调节。然而,丝切蛋白调节的肌动蛋白动力学在记忆消除过程中的作用尚不清楚。在这里,我们观察到条件性味觉厌恶(CTA)记忆的消除导致大鼠边缘下皮层(IrL)中 ADF/丝切蛋白活性的时间依赖性增强。此外,IrL 中 ADF/丝切蛋白活性的时间性升高可以通过促进 AMPAR 突触表面募集来加速 CTA 记忆的消除,而 ADF/丝切蛋白活性的抑制则会破坏 AMPAR 突触表面运输并损害记忆的消除。最后,我们观察到 ADF/丝切蛋白调节的突触可塑性与突触后棘突的形态变化没有直接联系。这些发现可能有助于我们理解 ADF/丝切蛋白调节的肌动蛋白动力学在记忆消除中的作用,并表明适当操纵 ADF/丝切蛋白的活性可能是治疗记忆障碍的一种合适方法。