Yamanaka Manabu, Tian Zhen, Darvish-Ghane Soroush, Zhuo Min
Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi'an Jiaotong University, Shanxi, China Department of Physiology, Faculty of Medicine, University of Toronto, Ontario, Canada.
Department of Physiology, Faculty of Medicine, University of Toronto, Ontario, Canada.
Mol Pain. 2016 May 13;12. doi: 10.1177/1744806916647373. Print 2016.
The extracellular signal-regulated kinase is an important protein kinase for cortical plasticity. Long-term potentiation in the anterior cingulate cortex is believed to play important roles in chronic pain, fear, and anxiety. Previous studies of extracellular signal-regulated kinase are mainly focused on postsynaptic form of long-term potentiation (post-long-term potentiation). Little is known about the relationship between extracellular signal-regulated kinase and presynaptic long-term potentiation (pre-long-term potentiation) in cortical synapses. In this study, we examined whether pre-long-term potentiation in the anterior cingulate cortex requires the activation of presynaptic extracellular signal-regulated kinase. We found that p42/p44 mitogen-activated protein kinase inhibitors, PD98059 and U0126, suppressed the induction of pre-long-term potentiation. By contrast, these inhibitors did not affect the maintenance of pre-long-term potentiation. Using pharmacological inhibitors, we found that pre-long-term potentiation recorded for 1 h did not require transcriptional or translational processes. Our results strongly indicate that the activation of presynaptic extracellular signal-regulated kinase is required for the induction of pre-long-term potentiation, and this involvement may explain the contribution of extracellular signal-regulated kinase to mood disorders.
细胞外信号调节激酶是一种对皮质可塑性至关重要的蛋白激酶。前扣带回皮质中的长时程增强被认为在慢性疼痛、恐惧和焦虑中发挥重要作用。以往关于细胞外信号调节激酶的研究主要集中在长时程增强的突触后形式（后长时程增强）。关于皮质突触中细胞外信号调节激酶与突触前长时程增强（前长时程增强）之间的关系，人们所知甚少。在本研究中，我们检测了前扣带回皮质中的前长时程增强是否需要突触前细胞外信号调节激酶的激活。我们发现，p42/p44丝裂原活化蛋白激酶抑制剂PD98059和U0126抑制了前长时程增强的诱导。相比之下，这些抑制剂并不影响前长时程增强的维持。使用药理学抑制剂，我们发现记录1小时的前长时程增强不需要转录或翻译过程。我们的结果有力地表明，突触前细胞外信号调节激酶的激活对于前长时程增强的诱导是必需的，并且这种参与可能解释了细胞外信号调节激酶对情绪障碍的作用。
