Neural System Dynamics & Gene Expression Supporting Successful Cognitive Aging

项目总结（见说明）： 该提案应用了一套新的认知，神经生物学和分子分析方法， 如何理解啮齿动物衰老模型中“认知储备”的概念。集成 本文设计了一组实验，旨在评估差异认知轨迹的机制 在大鼠寿命的三个不同阶段，即青年、中年和 老了这些实验利用了目前无法用于人类的技术，以及 那些可以（如认知测试和MRI成像方法）。这些方法尚未应用于 在啮齿类动物中的组合，并涉及整个大脑的高分辨率MRI成像，认知 检查与颞叶和额叶（海马）中的8个大脑区域相关的领域的测试 CA 1、CA 3、齿状回、下托、颞叶、嗅周皮质、内侧皮质、海马、 内嗅皮层;额叶区域前扣带和前边缘皮层），行为诱导，单细胞 在这8个区域的基因表达成像，并在4个海马亚区细胞特异性整体 转录组分析。这些程序将在大鼠中进行，所述大鼠是根据以下条件选择的： 行为表现得分为“高”、“中”或“低” 青年、中年和老年大鼠的分布。目前的实验有可能确定 细胞特异性RNA转录物和大脑区域中对认知至关重要的行为激活回路，以及 定义了个体如何在一生中沿着认知能力连续体沿着。的 这些方法的组合将使得能够识别与“更多”或“更少”相关的那些变量。 “不太”成功的认知老化轨迹-如果要有效治疗， 开发该项目的具体目标是在两个主要目标下进行实验。AIM 1是 识别海马亚区的转录模式，这些转录模式与不同的认知功能相关， 在整个生命周期中的能力倾向。目的2是确定行为诱导的活动模式，在颞叶和额叶 与不同认知能力相关的叶回路，以确定回路特征 与衰老过程中成功的认知结果以及颞叶和额叶 叶独立老化。总之，在这些实验中收集的数据应该确定有用的目标， 发展策略以优化老化过程中的认知。

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.