PDF(Pubmed)
Abstract：
Aging is associated with impairments in learning, memory, and cognitive flexibility, as well as a gradual decline in hippocampal neurogenesis. We investigated the performance of 6-and 14-month-old mice (considered mature adult and late middle age, respectively) in learning and memory tasks based on the Morris water maze (MWM) and determined their levels of preceding and current neurogenesis. While both age groups successfully performed in the spatial version of MWM (sMWM), the older mice were less efficient compared to the younger mice when presented with modified versions of the MWM that required a reassessment of the previously acquired experience. This was detected in the reversal version of MWM (rMWM) and was particularly evident in the context discrimination MWM (cdMWM), a novel task that required integrating various distal cues, local cues, and altered contexts and adjusting previously used search strategies. Older mice were impaired in several metrics that characterize rMWM and cdMWM, however, they showed improvement and narrowed the performance gap with the younger mice after additional training. Furthermore, we analyzed the adult-born mature and immature neurons in the hippocampal dentate gyrus and found a significant correlation between neurogenesis levels in individual mice and their performance in the tasks demanding cognitive flexibility. These results provide a detailed description of the age-related changes in learning and memory and underscore the importance of hippocampal neurogenesis in supporting cognitive flexibility.
摘要：
衰老与学习障碍有关，记忆,和认知灵活性，以及海马神经发生的逐渐下降。我们调查了6个月和14个月大的小鼠的表现（考虑成年和中年后期，分别）在基于莫里斯水迷宫（MWM）的学习和记忆任务中，并确定了其先前和当前神经发生的水平。虽然这两个年龄组都成功地在MWM的空间版本(sMWM)中进行了表演，当接受改良版本的MWM时,需要重新评估以前获得的经验,与年轻小鼠相比,年龄较大的小鼠的效率较低.这在MWM（rMWM）的逆转版本中检测到，在上下文区分MWM（cdMWM）中尤其明显，一项新的任务，需要整合各种远端线索，当地的线索,和改变上下文和调整以前使用的搜索策略。老年小鼠在表征rMWM和cdMWM的几个指标中受损，然而,在额外训练后，他们表现出改善，并缩小了与年轻小鼠的表现差距。此外，我们分析了成年出生的海马齿状回中的成熟和未成熟神经元，发现个体小鼠的神经发生水平与其在要求认知灵活性的任务中的表现之间存在显著的相关性。这些结果提供了与年龄相关的学习和记忆变化的详细描述，并强调了海马神经发生在支持认知灵活性方面的重要性。
