Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada.
Neurobiol Aging. 2018 Dec;72:134-146. doi: 10.1016/j.neurobiolaging.2018.08.020. Epub 2018 Aug 28.
Aging is associated with changes in executive functioning and the mesocorticolimbic dopamine system. However, the effects of aging on different forms of behavioral flexibility are not fully characterized. In young (∼5 months) and aged (∼22 months) male Fischer 344 × brown Norway rats, we assessed spatial working memory and different forms of behavioral flexibility using operant tasks: strategy set-shifting (study 1) or probabilistic reversal learning (study 2). We also assessed dopaminergic markers using immunohistochemistry. Compared with young rats, aged rats displayed impairments in working memory. Aged rats also showed nonperseverative impairments in set-shifting, with a subset also showing impairments in initial discrimination learning. In probabilistic reversal learning, aged rats completed more reversals, driven by an increased sensitivity to recent reward and negative feedback. Tyrosine hydroxylase (TH) showed region-specific changes with aging and was correlated with several measures of behavioral flexibility. These data suggest that age-related changes prefrontal cortical function and dopamine synthesis contribute to changes in executive functioning during aging.
衰老是与执行功能和中脑边缘多巴胺系统的变化相关的。然而，衰老对不同形式的行为灵活性的影响尚未完全阐明。在年轻（约 5 个月）和年老（约 22 个月）雄性 Fischer 344× 棕色挪威大鼠中，我们使用操作性任务评估了空间工作记忆和不同形式的行为灵活性：策略转换（研究 1）或概率反转学习（研究 2）。我们还使用免疫组织化学评估了多巴胺能标志物。与年轻大鼠相比，老年大鼠在工作记忆方面表现出损伤。老年大鼠在转换任务中还表现出非持续性的辨别学习障碍，一部分大鼠也表现出初始辨别学习障碍。在概率反转学习中，老年大鼠完成了更多的反转，这是由于对近期奖励和负反馈的敏感性增加所致。酪氨酸羟化酶（TH）随年龄发生了特定区域的变化，与几种行为灵活性测量值相关。这些数据表明，与年龄相关的前额叶皮层功能和多巴胺合成变化导致了衰老过程中执行功能的变化。
