Laboratory of Behavioral Neuroscience, Neurocognitive Aging Section, National Institute on Aging, Baltimore, Maryland.
Hippocampus. 2019 Dec;29(12):1165-1177. doi: 10.1002/hipo.23130. Epub 2019 Jul 23.
Changes in neuronal network activity and increased interindividual variability in memory are among the most consistent features of growing older. Here, we examined the relationship between these hallmarks of aging. Young and aged rats were trained on a water maze task where aged individuals reliably display an increased range of spatial memory capacities relative to young. Two weeks later, neuronal activity was induced pharmacologically with a low dose of pilocarpine and control animals received vehicle. Activity levels were proxied by quantifying the immediate early gene products Arc and c-Fos. While no relationship was observed between basal, resting activity, and individual differences in spatial memory in any brain region, pilocarpine-induced marker expression was tightly coupled with memory in all areas of the prefrontal cortex (PFC) and hippocampus examined. The nature of this association, however, differed across regions and in relation to age-related cognitive outcome. Specifically, in the medial PFC, induced activity was greatest in aged rats with cognitive impairment and correlated with water maze performance across all subjects. In the hippocampus, the range of induced marker expression was comparable between groups and similarly coupled with memory in both impaired and unimpaired aged rats. Together the findings highlight that the dynamic range of neural network activity across multiple brain regions is a critical component of neurocognitive aging.
神经元网络活动的变化和记忆个体间变异性的增加是衰老过程中最一致的特征之一。在这里，我们研究了这些衰老标志之间的关系。年轻和老年大鼠在水迷宫任务中接受训练，而老年大鼠在空间记忆能力方面可靠地显示出比年轻大鼠更大的范围。两周后，用低剂量毛果芸香碱诱导神经元活性，而对照动物接受载体。通过定量即时早期基因产物 Arc 和 c-Fos 来代理活性水平。虽然在任何脑区都没有观察到基础、静息活动与空间记忆个体差异之间的关系，但毛果芸香碱诱导的标志物表达与前额叶皮层（PFC）和海马体所有区域的记忆紧密相关。然而，这种关联的性质因区域而异，也与与年龄相关的认知结果有关。具体来说，在 medial PFC 中，诱导的活性在认知障碍的老年大鼠中最大，并且与所有受试者的水迷宫表现相关。在海马体中，各组之间诱导的标记物表达范围相当，并且与受损和未受损的老年大鼠的记忆均相关。这些发现共同强调了多个脑区神经网络活动的动态范围是神经认知衰老的关键组成部分。
