Young M E, Ohm D T, Dumitriu D, Rapp P R, Morrison J H
Fishberg Department of Neuroscience, The Friedman Brain Institute, Kastor Neurobiology of Aging Laboratory, and The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD 21224, USA.
Neuroscience. 2014 Aug 22;274:33-43. doi: 10.1016/j.neuroscience.2014.05.008. Epub 2014 May 20.
Aging decreases the density of spines and the proportion of thin spines in the non-human primate (NHP) dorsolateral prefrontal cortex (dlPFC). In this study, we used confocal imaging of dye-loaded neurons to expand upon previous results regarding the effects of aging on spine density and morphology in the NHP dlPFC and compared these results to the effects of aging on pyramidal neurons in the primary visual cortex (V1). We confirmed that spine density, and particularly the density of thin spines, decreased with age in the dlPFC of rhesus monkeys. Furthermore, the average head diameter of non-stubby spines in the dlPFC was a better predictor than chronological age of the number of trials required to reach criterion on both the delayed response test of visuospatial working memory and the delayed nonmatching-to-sample test of recognition memory. By contrast, total spine density was lower on neurons in V1 than in dlPFC, and neither total spine density, thin spine density, nor spine size in V1 was affected by aging. Our results highlight the importance and selective vulnerability of dlPFC thin spines for optimal prefrontal-mediated cognitive function. Understanding the nature of the selective vulnerability of dlPFC thin spines as compared to the resilience of thin spines in V1 may be a promising area of research in the quest to prevent or ameliorate age-related cognitive decline.
衰老会降低非人类灵长类动物（NHP）背外侧前额叶皮层（dlPFC）中棘突的密度以及细棘突的比例。在本研究中，我们使用对染料加载神经元的共聚焦成像技术，以拓展先前关于衰老对NHP dlPFC中棘突密度和形态影响的研究结果，并将这些结果与衰老对初级视觉皮层（V1）中锥体神经元的影响进行比较。我们证实，恒河猴dlPFC中的棘突密度，尤其是细棘突的密度，会随着年龄增长而降低。此外，在视觉空间工作记忆的延迟反应测试和识别记忆的延迟非匹配样本测试中，dlPFC中非粗短棘突的平均头部直径比实际年龄更能预测达到标准所需的试验次数。相比之下，V1中神经元的总棘突密度低于dlPFC，并且衰老对V1中的总棘突密度、细棘突密度或棘突大小均无影响。我们的研究结果突出了dlPFC细棘突对于最佳前额叶介导的认知功能的重要性和选择性易损性。了解与V1中细棘突的韧性相比，dlPFC细棘突选择性易损性的本质，可能是预防或改善与年龄相关的认知衰退研究中一个有前景的领域。
