Bidirectional Structural and Functional Plasticity in the Aging Brain.

衰老的过程会对个人的认知能力产生负面影响，然而个体之间存在显著的差异，其原因是争论的主题。我们建议研究运动如何影响老年大脑的两个理论概念，认知能力和认知储备。认知能力是一个术语，指的是我们如何学习、记忆和解决问题的机制，可以通过行为测试或电生理分析来评估。认知储备用于描述优化或促进老年大脑神经弹性的因素，有助于促进更高水平的认知功能。有人提出，大脑结构的增加可能会增强认知储备。***有大量证据表明，运动可以提高认知能力和认知储备，然而，运动益处的机制仍有待充分阐明。在这些实验中，我们将确定在增强认知能力和储备方面，早期锻炼是否比晚期锻炼更有效，或者是否需要终身锻炼。这些实验将利用多种实验方法（电生理、免疫组织化学、生化、行为学）来研究结构和功能变化在优化衰老大脑认知能力和认知储备中所起的作用。***我研究的长期目标是了解在发育过程中不同时间点的锻炼对男性和女性大脑可塑性的不同影响，以及这与一生中学习和记忆过程的关系。***本研究计划的短期目标是：(1)确定早期生活经验对于增强老年大脑的认知功能是否必要，这是一种索引认知储备的方式；(2)确定老年人增加运动是否有同样的好处，或者(3)是否需要终身锻炼来优化认知储备。为了检验这些目标，我们将采用几种我们提出的新方法，这些方法可以帮助我们区分老年大脑的认知能力和认知储备。其中包括引入一种改良的狂犬病毒介导的追踪系统，以检查老年大脑中齿状颗粒细胞的神经支配，考虑到它们是在生命早期（发育性神经发生）产生还是在成年后期（成年神经发生）产生。这将使我们能够确定生命早期增强的神经发生是否增强了认知储备，并产生了一群神经元，这些神经元可以在老年大脑中使用，以根据需要增强认知能力。

The process of aging can negatively impact an individual's cognitive capacity, however there is significant variability across individuals and the reasons for this are the subject of debate. We propose to look at how exercise can impact two theoretical concepts, cognitive capacity and cognitive reserve, in the aged brain. Cognitive capacity is a term that refers to the mechanisms that underlie how we learn, remember and problem solve, and can be assessed using either behavioral tests or electrophysiological analyses. Cognitive reserve is used to describe factors that optimize or promote neurological resiliency in the aged brain, helping to promote higher levels of cognitive functioning. It has been proposed that increases in brain structure may enhance cognitive reserve.***There is considerable evidence that exercise can improve both cognitive capacity and cognitive reserve, however the mechanisms responsible for the benefits of exercise remain to be fully elucidated. In these experiments we will determine if early exposure to exercise is more effective than late exposure to exercise in enhancing cognitive capacity and reserve, or whether life-long exposure is needed. These experiments will utilize multiple experimental approaches (electrophysiological, immunohistochemical, biochemical, behavioral) to develop convergent evidence for the roles structural and functional changes play in optimizing cognitive capacity and cognitive reserve in the aging brain. ***The long-term objective of my research my research program will be to understand how exercise at different time points during development impacts different measures of brain plasticity in the male and female brain and how this relates to learning and memory processes across the lifespan. ***The short-term objectives specific to this research proposal are to: (1) determine whether early life experience is necessary for enhanced cognitive functioning in the aged brain, a way of indexing cognitive reserve; (2) determine whether increased activity in aged populations can have the same benefits, or (3) whether life-long exposure to exercise is required to optimize cognitive reserve. ***To examine these objectives we will employ several novel approaches that we propose can help us differentiate between cognitive capacity and cognitive reserve in the aged brain. Among these will be the introduction a modified rabies virus-mediated tracing system to examine the innervation of dentate granule cells in the aged brain, taking into account whether they were generated early in life (developmental neurogenesis) or later on in adulthood (adult neurogenesis). This will allow us to determine if enhanced neurogenesis early in life enhances cognitive reserve, and produces a population of neurons that can be used in the aged brain to enhance cognitive capacity on demand.