Functional Aspects of Adult Hippocampal Neurogenesis

描述（由申请人提供）：成年哺乳动物海马体含有在成年期分化为神经元的前体细胞。这种现象被称为成人神经发生。这项研究的目的是探讨成年人海马体中形成的神经元是否会影响行为，海马体是一个参与学习和记忆的大脑区域。四个假设的预测将被测试。学习假说认为，成年海马神经发生在获得海马依赖性行为中起作用。因此，根据学习假说，增加神经发生的因素应该改善学习。遗忘假说认为，新的海马神经元有助于遗忘，而增加神经发生的因素会干扰海马依赖行为的长期保持。自我修复假说认为，新形成的神经元修复受损的海马电路，并预测增加神经发生的因素将改善海马损伤后的功能恢复。相反，损伤过程假说认为，海马损伤后形成的新神经元会干扰剩余的完整海马组织的功能。因此，损伤假说预测，增加海马神经发生的因素将加剧海马损伤引起的行为障碍。用于测试这些假设的方法将涉及使用大鼠作为实验对象来研究学习和记忆。将使用选择性5-羟色胺再摄取抑制剂氟西汀和运动（跑轮）控制海马神经发生。将使用免疫组织化学方法（包括BrdU-、NeuN-、GFAP-和双皮质素标记）、共聚焦激光显微镜和无偏体视学方法定量神经发生。拟议的研究将提供有关成人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。

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.