Nicolle Michelle M, Baxter Mark G
Department of Neuroscience, Mayo Graduate School, Mayo Clinic, 310 Birdsall Bldg, 4500 San Pablo Rd, Jacksonville, FL 32224, USA.
Eur J Neurosci. 2003 Dec;18(12):3335-42. doi: 10.1111/j.1460-9568.2003.03077.x.
Aged Long-Evans rats exhibit deficits in attentional set shifting, an aspect of executive function, relative to adult rats. Impairments in set shifting and spatial learning are uncorrelated in aged rats, indicating a possible dissociation of the effects of ageing in prefrontal versus hippocampal systems. Ionotropic glutamate receptor binding was assessed using an in vitro autoradiography method in young and aged rats. The rats had been tested on a set-shifting task that measured attentional set shifts and reversal learning, as well as in a spatial learning task in the Morris water maze. [3H]Kainate, [3H]AMPA and NMDA-displaceable [3H]glutamate receptor binding were quantified in orbital cortex, cingulate cortex, medial frontal cortex, dorsolateral and dorsomedial striatum. Age-related decreases in [3H]kainate binding were apparent in all regions measured. Similarly, NMDA-displaceable [3H]glutamate binding was decreased in the aged rats in all the regions measured except for the medial frontal area where no age effects were observed. [3H]AMPA receptor binding was preserved with age in all the regions measured. Lower levels of [3H]kainate binding in the cingulate cortex were significantly correlated with poorer set-shifting performance, whereas higher levels of NMDA binding in the dorsomedial striatum were correlated with poorer set-shifting performance. There were no significant correlations between the levels of ionotropic glutamate receptors and performance in the reversal task or spatial learning in the Morris water maze. These results indicate that age-related behavioural deficits in attentional set shifting are selectively associated with neurobiological alterations in the cingulate cortex and dorsomedial striatum.
与成年大鼠相比，老年Long-Evans大鼠在注意力集转换（执行功能的一个方面）方面存在缺陷。在老年大鼠中，集转换和空间学习的损伤不相关，这表明前额叶与海马体系统中衰老效应可能存在分离。使用体外放射自显影法评估年轻和老年大鼠的离子型谷氨酸受体结合情况。这些大鼠接受了一项集转换任务测试，该任务测量注意力集转换和逆向学习，以及在莫里斯水迷宫中的空间学习任务。在眶额皮质、扣带回皮质、内侧前额叶皮质、背外侧和背内侧纹状体中对[3H]海人藻酸、[3H]α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和NMDA可置换的[3H]谷氨酸受体结合进行了定量分析。在所测量的所有区域中，[3H]海人藻酸结合均出现与年龄相关的下降。同样，除内侧前额叶区域未观察到年龄效应外，老年大鼠在所测量的所有区域中，NMDA可置换的[3H]谷氨酸结合均下降。在所测量的所有区域中，[3H]AMPA受体结合随年龄保持不变。扣带回皮质中较低水平的[3H]海人藻酸结合与较差的集转换表现显著相关，而背内侧纹状体中较高水平的NMDA结合与较差的集转换表现相关。离子型谷氨酸受体水平与逆向任务表现或莫里斯水迷宫中的空间学习之间无显著相关性。这些结果表明，注意力集转换中与年龄相关的行为缺陷与扣带回皮质和背内侧纹状体中的神经生物学改变选择性相关。
