Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, Maryland, USA.
Hippocampus. 2024 Feb;34(2):88-99. doi: 10.1002/hipo.23591. Epub 2023 Dec 11.
The hippocampal formation is vulnerable to the process of normal aging. In humans, the extent of this age-related deterioration varies among individuals. Long-Evans rats replicate these individual differences as they age, and therefore they serve as a valuable model system to study aging in the absence of neurodegenerative diseases. In the Morris water maze, aged memory-unimpaired (AU) rats navigate to remembered goal locations as effectively as young rats and demonstrate minimal alterations in physiological markers of synaptic plasticity, whereas aged memory-impaired (AI) rats show impairments in both spatial navigation skills and cellular and molecular markers of plasticity. The present study investigates whether another cognitive domain is affected similarly to navigation in aged Long-Evans rats. We tested the ability of young, AU, and AI animals to recognize novel object-place-context (OPC) configurations and found that performance on the novel OPC recognition paradigm was significantly correlated with performance on the Morris water maze. In the first OPC test, young and AU rats, but not AI rats, successfully recognized and preferentially explored objects in novel OPC configurations. In a second test with new OPC configurations, all age groups showed similar OPC associative recognition memory. The results demonstrated similarities in the behavioral expression of associative, episodic-like memory between young and AU rats and revealed age-related, individual differences in functional decline in both navigation and episodic-like memory abilities.
海马结构容易受到正常衰老过程的影响。在人类中,这种与年龄相关的恶化程度因人而异。长时程增强大鼠随着年龄的增长复制了这些个体差异,因此它们是研究无神经退行性疾病衰老的有价值的模型系统。在 Morris 水迷宫中,记忆未受损的老年(AU)大鼠能够像年轻大鼠一样有效地导航到记忆中的目标位置,并且在突触可塑性的生理标志物方面表现出最小的变化,而记忆受损的老年(AI)大鼠在空间导航技能以及可塑性的细胞和分子标志物方面均表现出损伤。本研究调查了另一个认知领域是否与长时程增强大鼠的导航相似受到影响。我们测试了年轻、AU 和 AI 动物识别新物体-位置-上下文(OPC)配置的能力,发现新颖 OPC 识别范式的表现与 Morris 水迷宫的表现显著相关。在第一个 OPC 测试中,年轻和 AU 大鼠成功地识别了新的 OPC 配置中的物体并优先探索了这些物体,但 AI 大鼠则不然。在第二个使用新 OPC 配置的测试中,所有年龄组均表现出类似的 OPC 联想记忆。结果表明,年轻和 AU 大鼠在联想、类似情节记忆的行为表达上存在相似性,并揭示了导航和类似情节记忆能力的功能下降存在与年龄相关的个体差异。