成年大鼠恐惧记忆新机制的研究

项目名称： 成年大鼠恐惧记忆新机制的研究

项目编号： No.30860089

项目类型： 地区科学基金项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 蒋丽珠

作者单位： 大理学院

项目金额： 25万元

中文摘要： 恐惧性刺激可导致认知功能尤其是记忆功能的损害，但关于恐惧性刺激导致记忆损害的具体神经生物学机制目前仍不十分清楚。杏仁核、海马是脑内参与恐惧等情绪学习记忆的主要核团，成年海马新生神经元的功能已得到广泛认同，杏仁核、海马新生神经元结构与功能的改变可能是导致这种记忆损害的重要神经生物学机制。本项目探索了杏仁核、海马新生神经细胞分化及功能的变化是否为导致恐惧记忆长期存在的神经生物学机制。主要进展如下：1）条件恐惧刺激后大鼠僵立行为明显增高，并伴随着海马齿状回、杏仁核区BrdU阳性细胞数减少；2）条件恐惧刺激后大鼠海马齿状回、杏仁核区新生神经细胞分化为神经元的百分比减少、分化为星型胶质细胞的百分比增加；3）x-ray抑制了大鼠海马齿状回、SVZ新生神经细胞增殖，并伴随着大鼠僵立行为减弱；4）氟西汀促进大鼠室管膜下区、海马齿状回新生神经细胞增殖，部分逆转了大鼠条件恐惧刺激所致的新生神经细胞分化比例的改变，但对条件恐惧刺激后大鼠僵立行为无明显影响。以上进展为海马齿状回、杏仁核新生神经细胞与恐惧记忆提供了有力证据，即上述两个脑区新生神经细胞增殖、分化及功能的改变仅在一定条件下与恐惧记忆长期保存有关。

中文关键词： 大鼠；杏仁核；海马；恐惧记忆；新生神经元

英文摘要： Fear conditioned stimuli can impair congnitive function especially memory function, but the specific neurobiological mechanism remain unclear. Amygdala and hippocampus are key neuronal substrates which involved in emotional learning, such as fear.The function of adult born neurons in hippocampus have been widely identified, changes of structures and functions of adult born neurons in amygdala and hippocampus may underlie the memory impairment. Thus, the present project has explored whether changes of adult neurogenesis in amygdala and hippocampus underlie the neurobiological mechanism of memory impairment. The major results are as following 1)Fear conditioned stimuli caused distinctive freezing in rats and accompanied obviously decreasing of BrdU postive cells in dentate gyrus(DG) and amygdala. 2)Fear conditioned stimuli lead to changes the differentiation of adult born cells, that is the percent of adult born cells differentiate into neuron decreased, and differentiate into astroglia increased. 3)x-ray suppressed adult neurogenesis, and accompanied reduce of freezing in rats. 4）Fluoxetine promote adult neurogenesis, and partly rescued the changes of adult born cells differentiation, but there is no obviously changes of freezing in rats are observed. These results demonstrate the evidence that only under special conditions adult neurogenesis in dentate gyrus and amygdala have relationship with long term existing of fear memory.

英文关键词： adult rat; amygdala; hippocampus; fear memory; neurogenesis