Genotypic/phenotypic mediators of synaptic plasticity in aging

大量的研究工作投入，以揭示一些与年龄相关的认知功能变化的机制，特别是那些有关过早的记忆和学习衰退。研究发现，易受年龄影响的大脑区域的突触可塑性受损最能预测衰老中的认知能力下降。直到最近，关于人类神经元可塑性的推断只能从可塑性的间接测量中得出，例如认知功能的变化。然而，非侵入性脑刺激技术的最新发展提供了多种研究工具，允许直接评估人类皮层区域的突触可塑性机制。我们小组的工作表明，用这些脑刺激技术评估的突触可塑性与功能相关的脑功能的变化显著相关。使用这些创新的大脑刺激技术的主要兴趣之一在于它们被证明能够产生持久的大脑可塑性改善。也许最重要的是，这些长期的后遗症被证明与持久的行为益处有关。 * 在拟议的研究计划中进行的工作将利用最新和最先进的脑刺激技术，以非侵入性方式探测随着年龄增长而功能下降的潜在可塑性机制。* 除了对知识进步的重大贡献外，旨在恢复老龄人口大脑可塑性的干预方案也可能被证明对有患老年性神经退行性疾病（如阿尔茨海默病）风险的人具有保护作用。 **

Considerable research efforts are invested to shed some light on the mechanisms underlying cognitive function changes associated with age, particularly those pertaining to premature memory and learning decline. Impaired synaptic plasticity in age-susceptible brain regions was found to best predict cognitive decline in aging. Until recently, inferences about neuronal plasticity in humans could only be drawn from indirect measures of plasticity, such as cognitive function changes. The recent development of non-invasive brain stimulation techniques, however, provides a variety of research tools allowing the direct assessment of synaptic plasticity mechanisms in human cortical areas. Work from our group has shown that synaptic plasticity, as assessed with these brain stimulation techniques, are significantly linked with changes in functionally related brain functions. One of the major interests in using these innovative brain stimulation techniques resides in their proven capacity to generate durable brain plasticity improvements. Perhaps most importantly, these long-term after-effects were shown to be associated with lasting behavioural benefits. ****The work that will be conducted in the proposed research program will take advantage of the latest and most advanced brain stimulation techniques to noninvasively probe plasticity mechanisms underlying functional decline as people age. ****In addition to its significant contribution to knowledge advancement, intervention protocols aiming to restore brain plasticity in the aging population may also prove to be protective in people at risk of developing age-related neurodegenerative conditions such as Alzheimer's disease.****** **