一： 一种用于测试猕猴空间学习记忆能力的新迷宫模型的建立二： 大鼠海马在恐惧条件化和消退中作用的研究
文献类型：学位论文
| 作者 | 张波 |
| 答辩日期 | 2010-01-15 |
| 文献子类 | 博士 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 马原野 |
| 关键词 | 猕猴 空间 学习 记忆 迷宫 海马 微注射 胶质细胞 Nmda 恐惧条件化 恐惧消退 |
| 英文摘要 | Part one：Maze model to study spatial learning and memory in freely moving monkeys There is a cognitive map theory in cognitive neuroscience research: the spatial memory of humans and other animals is summarized in a map which is located in hippocampus of the brain. Results from researches in rodents are coincident with each other and all data support the theory. However, results from researches in non-human primates are not coincident with each other and that in rodents. This discrepancy is believed to due to different methods and equipments used in these two species. Maze models have been widely used in cognitive neuroscience researches in different species and proved to be efficient, but the existing mazes used in non-human primates all have their own shortcomings and limitations, therefore these mazes are not effective enough and well utilized. We design a maze model for non-human primates which has many advantages that could make up the shortcomings and limitations of the existing mazes and could be comparable with the mazes used in rodents, and it could test the cognitive ability of animals especially the spatial learning and memory ability of non-human primates. More importantly, our maze could test the cognitive ability of animals to acquire new spatial memory, therefore is helpful in the research of spatial cognition disorder in humans while none of the existing mazes has that function. Part two：The role of hippocampus in fear conditioning and extinction in rats In humans, after suffering from life-threatening and seriously traumatic incidents, excessive fear could lead to mentle called disease post-traumatic stress disorder (PTSD). Pavlovian fear conditioning and extinction model in rodents is a classic animal model for PTSD, and researches using this model are helpful for us to study the mechanism and to cure PTSD. In researches using this model to study fear memory, most experiments focus on two brain regions amygdala and prefrontal cortext and results from different experiments agree with each other. Hippocampus is a key brain region in learning and memory, but its role in fear memory especially cued fear memory is controversial and further studies are needed. Our researches explore the role of hippocampus in fear memory from two different aspects. Experiment 1 explores the role of hippocampal gliocyte in consolidation of fear memory by microinjection of fluorocitrate (a selective inhibitor of gliocyte) into hippocampus of rats. Experiment 2 explores the role of hippocampal NMDA receptor in cued fear extinction via microinjection of NMDA receptor antagonist MK-801 (dizocilpine) into hippocampus of rats. Experiment 1 shows that hippocampal gliocyte is involved in consolidation of fear memory and indicate different involvement in different kinds of fear memory. Experiment 2 shows that consolidation of fear memory is impaired by MK-801. Our two experiments all support the idea that hippocampus is involved in cued fear memory and help us to know more about the role of hippocampus in fear memory.; 第一部分：一种用于测试猕猴空间学习记忆能力的新迷宫模型的建立脑认知科学的认知地图理论认为：人或动物的空间记忆被描述在一张认知地图上，这张地图就被存储在大脑的海马中。利用啮齿类动物进行的研究得到的结论都是一致的，都支持这一理论。然而，利用非人灵长类动物进行的研究得出的结论彼此之间并不一致，和啮齿类动物之间的结论也不一致。这种不一致可能是由于在两种动物中运用了不同的实验装置和方法引起的。迷宫模型已经广泛地应用于不同动物的认知研究中，但是现存的应用于非人灵长类动物的迷宫，因为都有各自的一些缺点和局限性并不能得到有效地应用。因此，我们建立了一个新的迷宫模型，它避免了现存的应用于非人灵长类动物的迷宫的缺点和局限性，可以和在啮齿类动物中应用的迷宫相媲美，可以很好地应用于测试动物的认知能力，尤其是非人灵长类动物的空间学习记忆能力。同时，我们的迷宫模型可以测试动物学习新的空间关系的认知能力，从而有利于人类空间认知功能障碍的研究工作，这是现有的迷宫模型所不能做到的。第二部分：大鼠海马在恐惧条件化和消退中作用的研究在人类中，经历过对生命具有威胁的事件或严重的创伤性事件后，过度的恐惧会导致一种精神疾病——创伤后应激障碍。在啮齿类动物中建立的巴甫洛夫恐惧条件化和消退模型是此疾病典型的动物模型，利用此模型进行的研究有利于我们了解创伤后应激障碍的神经机制和对其进行治疗。在利用此动物模型进行的恐惧记忆研究中，大部分实验集中于大脑的杏仁核和前额叶两个脑区的研究，得到的研究结论也比较一致。海马是参与学习记忆的一个关键脑区，但是对于其在恐惧记忆（尤其是线索性恐惧记忆）中的作用的研究结果并不一致，需要进行更加深入的研究。本部分两个实验从不同的侧面研究了海马在恐惧记忆中的作用：实验1通过向大鼠海马内微注射胶质细胞的特异性抑制剂氟代柠檬酸，来研究海马内的胶质细胞在恐惧记忆巩固过程中的作用；实验2通过向大鼠海马内微注射NMDA受体的抑制剂MK-801，来研究此受体在线索性恐惧消退中的作用。实验1结果显示海马内的胶质细胞在恐惧记忆的巩固过程中起作用，同时提示其在不同类型的恐惧记忆的巩固中起到了不同的作用；实验2结果显示MK-801损伤了恐惧消退记忆的巩固过程。两个实验都支持海马参与了线索性恐惧记忆这一观点，加深了我们对海马在恐惧记忆中功能的认识。 |
| 语种 | 中文 |
| 公开日期 | 2010-11-12 |
| 源URL | [http://159.226.149.42:8088/handle/152453/6472]  |
| 专题 | 昆明动物研究所_认知障碍病理学 |
| 推荐引用方式 GB/T 7714 | 张波. 一： 一种用于测试猕猴空间学习记忆能力的新迷宫模型的建立二： 大鼠海马在恐惧条件化和消退中作用的研究[D]. 北京. 中国科学院研究生院. 2010. |
入库方式： OAI收割
来源：昆明动物研究所
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