Functional Aspects of Adult Hippocampal Neurogenesis

描述（由申请人提供）：成年哺乳动物海马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。拟议的研究探讨了在成人海马体中形成的神经元是否会影响行为，海马体是大脑中涉及学习和记忆的区域。四种假设的预测将被检验。学习假说认为，成人海马神经发生在海马依赖行为的习得中起作用。因此，根据学习假说，促进神经发生的因素应该能促进学习。遗忘假说认为，新的海马神经元有助于遗忘，增加神经发生的因素将干扰海马依赖行为的长期保留。自我修复假说认为，新形成的神经元可以修复受损的海马回路，并预测增加神经发生的因素将促进海马损伤后功能的恢复。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会加剧海马损伤引起的行为障碍。用于验证这些假设的方法将包括用老鼠作为实验对象来研究学习和记忆。海马神经发生将通过选择性5 -羟色胺再摄取抑制剂、氟西汀和运动（轮式跑步）来控制。神经发生将使用免疫组织化学方法进行量化，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。这些研究将提供关于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促进还是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.