Neural System Dynamics & Gene Expression Supporting Successful Cognitive Aging

项目总结(见说明)： 这项提议应用了一套新的认知、神经生物学和分子图谱方法来 如何理解啮齿动物衰老模型中“认知储备”的概念。一个完整的 设计了一套实验来评估不同认知轨迹背后的机制 在幼年、中年和成年三个不同的生命阶段观察大鼠的寿命 年长的。这些实验利用了目前无法在人类身上使用的技术，以及 那些能够做到的(如认知测试和磁共振成像方法)。这些方法还没有应用于 在啮齿动物之前结合，并涉及高分辨率MRL成像的整个大脑，认知 检查与颞叶和额叶(海马区)8个脑区相关的区域的测试 CA1区、CA3区、齿状回和丘脑下部；颞叶皮质周围区和内侧区 内嗅皮层；额叶区前扣带回和前额叶皮质)，行为诱导，单细胞 这8个区域和4个海马亚区细胞特异性整体的基因表达成像 转录组分析。这些程序将在根据以下条件选择的大鼠身上进行 行为表现得分“高”、“一般”或“低”的 幼年、中年和老年大鼠的分布。目前的实验有可能识别出 大脑中对认知至关重要的区域中的细胞特异性RNA转录本和行为激活电路，以及 这定义了个体在一生中是如何沿着认知能力连续体分离的。这个 这些方法的组合将能够识别与“更多”或“更多”相关的变量 不太成功的认知老化轨迹-如果要有效的治疗，一个基本的必要性 发展起来的。这个项目的具体目标是在两个主要目标下进行实验的。目标1是 识别与差异认知相关的海马亚区转录模式 在整个生命周期内的能力。目标2是确定行为诱导的颞叶和额叶的活动模式 与不同认知能力相关的脑叶回路，以识别什么是回路特征 与衰老期间成功的认知结果以及颞叶和额叶的程度有关 裂片独立老化。总而言之，在这些实验中收集的数据应该能识别出对 在衰老过程中优化认知的策略的发展。

PROJECT SUMMARY {See instructions): This proposal applies a novel set of cognitive, neurobiological and molecular profiling approaches to the question of how to understand the concept of "cognitive reserve" in a rodent model of aging. An integrated set of experiments is proposed designed lo assess, mechanisms underlying differential cognitive trajectories observed over the lifespan of the rat at three different phases of the lifespan, young adult, middle age, and old. The experiments take advantage of technologies that cannot be used in humans at present, as well as those that can (such as cognitive tests and MRl imaging methods). These methods have not been applied in combination in the rodent previously, and involve high resolution MRl Imaging of the entire brain, cognitive tests that examine domains relevant to 8 brain regions in the temporal and frontal lobes (hippocampal regions CAI, CA3, dentate gyrus and the subiculum; temporal lobe regions perirhinal cortex and medial entorhinal cortex; frontal lobe regions anterior cingulate and prelimbic cortex), behavior-induced, single cell gene expression imaging in these 8 regions, and in 4 hippocampal subregions cell-specific whole transcriptome analyses. These procedures will be conducted in rats that are chosen on the basis of possessing behavioral performance scores that are "high", "average" or "low" with respect to performance distributions from young, middle-aged and old rats. The present experiments have the potential to identify cell-specific RNA transcripts and behavior-activated circuits in brain regions that are critical for cognition, and that define how individuals segregate along a cognitive competence continuum throughout life. The combination of these methods will enable identification of those variables that are associated with "more" or "less" successful cognitive aging trajectories - a fundamental necessity if effective treatments are to be developed. The specific goals of this project are approached experimentally under two main aims. AIM 1 is to identify transcriptional patterns in hippocampal subregions that are associated with differential cognitive aptitudes across the lifespan. AIM 2 is to identify behavior-induced activity patterns in temporal and frontal lobe circuits associated with differential cognitive abilities, to identify what circuit characteristics are associated with successful cognitive outcomes during aging and the extent to which temporal and frontal lobes age independently. Together, the data collected in these experiments should identify targets useful in the development of strategies to optimize cognition during aging.