Luo Fei, Zheng Jian, Sun Xuan, Deng Wei-Ke, Li Bao Ming, Liu Fang
Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China.
Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China; Department of Forensic Medicine, Medical College of Nanchang University, Nanchang 330031, China.
Brain Res. 2017 Apr 15;1661:88-99. doi: 10.1016/j.brainres.2017.02.010. Epub 2017 Feb 16.
Neural mechanism underlying memory retrieval has been extensively studied in the hippocampus and amygdala. However, little is known about the role of medial prefrontal cortex in long-term memory retrieval. We evaluate this issue in one-trial step-through inhibitory avoidance (IA) paradigm. Our results showed that, 1) inactivation of mPFC by local infusion of GABA-receptor agonist muscimol caused severe deficits in retrieval of 1-day and 7-day but had no effects on 2-h inhibitory avoidance memory; 2) the protein level of phosphorylated-ERK1/2 in mPFC were significantly increased following retrieval of 1-day and 7-day IA memory, so did the numbers of phosphorylated-ERK (pERK) and phosphorylated-CREB (pCREB) labeled neurons; 3) intra-mPFC infusion of ERK kinase inhibitor PD98095 significantly reduced phosphorylated ERK1/2 levels and phosphorylated-ERK1/2 and phosphorylated-CREB labeled cells, and severely impaired retrieval of 7-day IA memory when the drugs were administrated 30min prior to test. The present study provides evidence that retrieval of long-lasting memory for inhibitory avoidance requires mPFC and involves the ERK-CREB signaling cascade.
记忆提取的神经机制已在海马体和杏仁核中得到广泛研究。然而，关于内侧前额叶皮质在长期记忆提取中的作用却知之甚少。我们在单次通过抑制性回避（IA）范式中评估了这个问题。我们的结果表明，1）通过局部注射GABA受体激动剂蝇蕈醇使内侧前额叶皮质失活会导致1天和7天记忆提取出现严重缺陷，但对2小时抑制性回避记忆没有影响；2）在1天和7天IA记忆提取后，内侧前额叶皮质中磷酸化ERK1/2的蛋白水平显著升高，磷酸化ERK（pERK）和磷酸化CREB（pCREB）标记的神经元数量也显著增加；3）在测试前30分钟向内侧前额叶皮质内注射ERK激酶抑制剂PD98095可显著降低磷酸化ERK1/2水平以及磷酸化ERK1/2和磷酸化CREB标记的细胞数量，并严重损害7天IA记忆的提取。本研究提供了证据表明，抑制性回避的长期记忆提取需要内侧前额叶皮质并涉及ERK-CREB信号级联反应。
