Curlik Daniel M, Weiss Craig, Nicholson Daniel A, Disterhoft John F
Department of Physiology, Feinberg School of Medicine, Northwestern University.
Department of Neurological Sciences, Rush University Medical Center.
Behav Neurosci. 2014 Dec;128(6):676-88. doi: 10.1037/bne0000018.
Age-related cognitive impairments are particularly prevalent in forms of learning that require a functionally intact hippocampal formation, such as spatial and declarative learning. However, there is notable heterogeneity in the cognitive abilities of aged subjects. To date, few studies have determined whether age-related impairments on one learning task relate to impairments on different learning tasks that engage overlapping cognitive processes. Here, we hypothesized that aged animals that were impaired on 1 hippocampal-dependent behavioral procedure would be impaired on a second hippocampal-dependent procedure. Conversely, aged animals that were unimpaired on 1 hippocampal-dependent task would be unimpaired with a subsequent hippocampal-dependent form of learning. To test these hypotheses, we trained young (2-3 months old) and aged (28-29 months old) F344XBN male rats with trace eyeblink conditioning, followed by the Morris water maze. Half of aged rats were impaired during trace conditioning. Nearly half of aged animals were also impaired during water maze probe testing. Performance during trace conditioning correlated with performance during water maze testing in aged animals. Further analyses revealed that, as a group, aged animals that were impaired on 1 hippocampal-dependent task were impaired on both tasks. Conversely, aged animals that were unimpaired on 1 task were unimpaired on both tasks. Together, these results suggest that aged-related impairments on 1 hippocampal-dependent task predict age-related impairments on a second hippocampal-dependent procedure. These results have implications for assigning personalized therapeutics to ameliorate age-related cognitive decline.
与年龄相关的认知障碍在需要功能完整的海马结构的学习形式中尤为普遍，例如空间学习和陈述性学习。然而，老年受试者的认知能力存在显著的异质性。迄今为止，很少有研究确定一项学习任务中与年龄相关的损伤是否与涉及重叠认知过程的不同学习任务中的损伤有关。在这里，我们假设在一项海马依赖性行为程序中受损的老年动物在第二项海马依赖性程序中也会受损。相反，在一项海马依赖性任务中未受损的老年动物在随后的海马依赖性学习形式中也不会受损。为了验证这些假设，我们用痕迹眨眼条件反射训练年轻（2 - 3个月大）和老年（28 - 29个月大）的F344XBN雄性大鼠，然后进行莫里斯水迷宫实验。一半的老年大鼠在痕迹条件反射训练中受损。在水迷宫探测测试中，近一半的老年动物也受损。老年动物在痕迹条件反射训练中的表现与在水迷宫测试中的表现相关。进一步分析表明，总体而言，在一项海马依赖性任务中受损的老年动物在两项任务中都受损。相反，在一项任务中未受损的老年动物在两项任务中都未受损。总之，这些结果表明，一项海马依赖性任务中与年龄相关的损伤预示着第二项海马依赖性程序中与年龄相关的损伤。这些结果对于分配个性化治疗方法以改善与年龄相关的认知衰退具有重要意义。
