Barense Morgan D, Fox Matthew T, Baxter Mark G
Department of Psychology, Harvard University, Cambridge, Massachusetts 02138, USA.
Learn Mem. 2002 Jul-Aug;9(4):191-201. doi: 10.1101/lm.48602.
Normal aging is associated with disruption of neural systems that subserve different aspects of cognitive function, particularly in the hippocampus and frontal cortex. Abnormalities in hippocampal function have been well investigated in rodent models of aging, but studies of frontal cortex function in aged rodents are few. We tested young (4-5 mo old) and aged (27-28 mo old) male Long-Evans rats on an attentional set-shifting task modified slightly from previous publication. After training on two problems in which the reward was consistently associated with the same stimulus dimension, and a reversal of one problem, a new problem was presented in which the reward was consistently associated with the previously irrelevant stimulus dimension (extradimensional shift [EDS]). Aged rats as a group were significantly impaired on the EDS, although some individual aged rats performed as well as young rats on this phase. In addition, some aged rats were impaired on the reversal, although a group effect did not reach significance in this phase. Impairment in neither reversal nor EDS was associated with impairments in spatial learning in the Morris water maze. Young rats with neurotoxic lesions of medial frontal cortex are also selectively impaired on the EDS. These results indicate that normal aging in rats is associated with impaired medial frontal cortex function. Furthermore, age-related declines in frontal cortex function are independent of those in hippocampal function. These results provide a possible basis for correlating age-related changes in neurobiological markers in frontal cortex with cognitive decline.
正常衰老与服务于认知功能不同方面的神经系统紊乱有关，尤其是在海马体和额叶皮质。在衰老的啮齿动物模型中，海马体功能异常已得到充分研究，但对老年啮齿动物额叶皮质功能的研究较少。我们对年轻（4 - 5月龄）和老年（27 - 28月龄）雄性Long-Evans大鼠进行了一项注意力转换任务测试，该任务是在之前发表的基础上稍作修改。在对两个奖励始终与同一刺激维度相关的问题进行训练，以及对其中一个问题进行反转后，呈现一个新问题，其中奖励始终与之前无关的刺激维度相关（维度转换[EDS]）。老年大鼠作为一个群体在EDS上显著受损，尽管一些老年个体在这一阶段的表现与年轻大鼠一样好。此外，一些老年大鼠在反转任务上受损，尽管在这一阶段群体效应未达到显著水平。反转任务和EDS任务的损伤均与莫里斯水迷宫中的空间学习损伤无关。内侧额叶皮质有神经毒性损伤的年轻大鼠在EDS上也有选择性损伤。这些结果表明，大鼠的正常衰老与内侧额叶皮质功能受损有关。此外，额叶皮质功能与年龄相关的下降独立于海马体功能的下降。这些结果为将额叶皮质中与年龄相关的神经生物学标志物变化与认知衰退相关联提供了可能的基础。
