Shors Tracey J, Townsend David A, Zhao Mingrui, Kozorovitskiy Yevgenia, Gould Elizabeth
Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey 08854-8020, USA.
Hippocampus. 2002;12(5):578-84. doi: 10.1002/hipo.10103.
The hippocampal formation generates new neurons throughout adulthood. Recent studies indicate that these cells possess the morphology and physiological properties of more established neurons. However, the function of adult generated neurons is still a matter of debate. We previously demonstrated that certain forms of associative learning can enhance the survival of new neurons and a reduction in neurogenesis coincides with impaired learning of the hippocampal-dependent task of trace eyeblink conditioning. Using the toxin methylazoxymethanol acetate (MAM) for proliferating cells, we tested whether reduction of neurogenesis affected learning and performance associated with different hippocampal dependent tasks: spatial navigation learning in a Morris water maze, fear responses to context and an explicit cue after training with a trace fear paradigm. We also examined exploratory behavior in an elevated plus maze. Rats were injected with MAM (7 mg/kg) or saline for 14 days, concurrent with BrdU, to label new neurons on days 10, 12, and 14. After treatment, groups of rats were tested in the various tasks. A significant reduction in new neurons in the adult hippocampus was associated with impaired performance in some tasks, but not with others. Specifically, treatment with the antimitotic agent reduced the amount of fear acquired after exposure to a trace fear conditioning paradigm but did not affect contextual fear conditioning or spatial navigation learning in the Morris water maze. Nor did MAM treatment affect exploration in the elevated plus maze. These results combined with previous ones suggest that neurogenesis may be associated with the formation of some but not all types of hippocampal-dependent memories.
海马结构在成年期会持续产生新的神经元。最近的研究表明，这些细胞具有更成熟神经元的形态和生理特性。然而，成年期产生的神经元的功能仍然存在争议。我们之前证明，某些形式的联想学习可以提高新神经元的存活率，而神经发生减少与海马体依赖的痕迹眨眼条件反射任务学习受损同时出现。我们使用毒素乙酸甲基偶氮甲醇（MAM）来增殖细胞，测试神经发生减少是否会影响与不同海马体依赖任务相关的学习和表现：在莫里斯水迷宫中的空间导航学习、对环境的恐惧反应以及在痕迹恐惧范式训练后对明确线索的恐惧反应。我们还在高架十字迷宫中检查了探索行为。给大鼠注射MAM（7毫克/千克）或生理盐水，持续14天，同时注射溴脱氧尿苷（BrdU），以在第10、12和14天标记新神经元。治疗后，对大鼠组进行各种任务测试。成年海马体中新神经元的显著减少与某些任务的表现受损有关，但与其他任务无关。具体而言，使用抗有丝分裂剂治疗会减少在接触痕迹恐惧条件反射范式后获得的恐惧量，但不影响莫里斯水迷宫中的情境恐惧条件反射或空间导航学习。MAM治疗也不影响高架十字迷宫中的探索。这些结果与之前的结果相结合表明，神经发生可能与某些但不是所有类型的海马体依赖记忆的形成有关。
