Functional Aspects of Adult Hippocampal Neurogenesis

成人海马神经发生的功能方面

基本信息

批准号：
6785955
负责人：
JULIAN R KEITH
金额：
$ 23.62万
依托单位：
UNIVERSITY OF NORTH CAROLINA WILMINGTON
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-08-01 至 2008-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The adult mammalian hippocampus contains precursor cells that differentiate into neurons during adulthood. This phenomenon is referred to as adult neurogenesis. The proposed studies address whether neurons that form in the adult hippocampus, a brain region involved in learning and memory, affect behavior. Predictions of four hypotheses will be tested. The learning hypothesis posits that adult hippocampal neurogenesis plays a role in the acquisition of hippocampus-dependent behavior. Thus, according to the learning hypothesis, factors that increase neurogenesis should improve learning. The forgetting hypothesis posits that new hippocampal neurons contribute to forgetting and that factors that increase neurogenesis will interfere with the long-term retention of hippocampus-dependent behavior. The self-repair hypothesis holds that newly formed neurons repair damaged hippocampal circuitry and predicts that factors that increase neurogenesis will improve recovery of function after hippocampal injury. The injury process hypothesis, in contrast, posits that new neurons that form in response to hippocampal injury interfere with the functioning of the remaining intact hippocampal tissue. Thus, the injury hypothesis predicts that factors that increase hippocampal neurogenesis will exacerbate the behavioral impairments caused by hippocampus damage. The methods used to test these hypotheses will involve studying learning and memory using rats as experimental subjects. Hippocampal neurogenesis will be controlled using the selective serotonin reuptake inhibitor, fluoxetine, and exercise (wheel running). Neurogenesis will be quantified using immunohistochemical methods including BrdU-, NeuN-, GFAP-, and doublecortin-labeling, confocal laser microscopy, and unbiased stereology methods. The proposed studies will provide important new information about the function of adult hippocampal neurogenesis and assess whether factors that increase the rate of neurogenesis enhance, or disrupt, recovery of hippocampal function after brain damage.

描述（由申请人提供）：成年哺乳动物海马包含成年期分化为神经元的前体细胞。该现象称为成人神经发生。拟议的研究介绍了成年海马形成的神经元是否会影响行为。将测试四个假设的预测。学习假设认为，成年海马神经发生在收购海马依赖性行为中起作用。因此，根据学习假设，增加神经发生的因素应改善学习。遗忘的假设表明，新的海马神经元有助于遗忘，而增加神经发生的因素将干扰海马依赖性行为的长期保留。自我修复假设认为，新形成的神经元修复会损害海马电路，并预测增加神经发生的因素将改善海马损伤后功能的恢复。相比之下，损伤过程假设表明，响应海马损伤的新神经元会干扰其余完整的海马组织的功能。因此，损伤假设预测，增加海马神经发生的因素将加剧由海马损伤引起的行为障碍。用于检验这些假设的方法将涉及使用大鼠作为实验学科研究学习和记忆。海马神经发生将使用选择性5-羟色胺再摄取抑制剂，氟西汀和运动（车轮运行）来控制。将使用包括BRDU-，Neun-，GFAP-和DoubleCortin-Labeling，共聚焦激光显微镜以及无偏置的立体学方法在内的免疫组织化学方法来定量神经发生。拟议的研究将提供有关成年海马神经发生功能的重要新信息，并评估增加神经发生率的因素是否会增强或破坏脑损伤后海马功能的恢复。