General Cognitive /Learning Deficits in Aged Mice

关于年龄相关学习缺陷的动物研究通常侧重于年龄对特定学习系统的影响。虽然信息量很大，但这项工作必然限制了关于衰老对一般认知/学习能力的影响的任何结论。这种对特定学习系统的关注严重影响了我们对年龄相关缺陷的理解，因为据估计，这种下降的25%-50%可归因于一般认知能力的损害，即超越特定学习系统或领域的能力。因此，阐明与年龄相关的认知缺陷的大脑基础需要一种概念上合理的方法，从影响特定(有限)领域的能力缺陷中解析出一般能力缺陷。如果不注意对学习/认知过程的普遍影响，随着年龄增长而导致的认知能力下降多达50% 必然得不到解释，从而减缓了有效治疗策略的发展。 在人类群体中，对个人学习能力的普遍影响反映了迄今发现的最显性的认知特征之一。然而，来自动物受试者的可比证据很少，而且在实验动物中从未描述过一般学习因素随年龄的变化。我们最近开发了一种独特的测试电池，它对小鼠的一般学习因素很敏感，这个因素在心理测量学上与人类的描述相当。在本提案的目标1和目标2中，我们总结了我们的计划，以表征从年轻到老年的实验室小鼠的一般学习/认知能力，并描述将提供初步迹象的分析方案 在一生中影响这些能力的不同变异性来源。这些研究是未来旨在阐明与年龄相关的一般认知/学习能力下降的大脑基础的工作的关键前奏。

Animal research on age-related learning deficits has typically focused on the impact of age on specific learning systems. While informative, this work necessarily limits any conclusions regarding the effects of aging on general cognitive/learning abilities. This focus on specific learning systems impacts critically on our understanding of age-related deficits, given that it is estimated that 25-50% of this decline is attributable to an impairment of general cognitive ability, i.e., an ability that transcends specific learning systems or domains. The elucidation of the brain substrates for age-related cognitive deficits thus requires a conceptually-sound approach from which to parse deficits in general abilities from those which impact specific (limited) domains. Absent any attention to general influences on learning/cognitive processes, as much as 50% of decline in cognitive abilities that accrue with aging will necessarily go unexplained, mitigating the development of effective treatment strategies. Among human populations, a general influence on individuals' learning abilities reflects one of the most dominant cognitive traits ever identified. However, comparable evidence from animal subjects is sparse, and age-dependent variations in general learning factors have never been described in laboratory animals. We have recently developed a unique test battery that is sensitive to a general learning factor in mice, and this factor is psychometrically comparable to that described in humans. In Aims 1 and 2 of the present proposal, we summarize our plans to characterize the general learning/cognitive abilities of laboratory mice that range in age from young to old, and describe analysis regimens that will provide preliminary indications of the differential sources of variability that impinge on these abilities across the life span. These studies are a critical prelude to future work directed at the elucidation of the brain substrates for age-related declines in general cognitive/learning abilities.