Genotypic/phenotypic mediators of synaptic plasticity in aging

人们投入了大量的研究工作，以揭示与年龄有关的认知功能变化的潜在机制，特别是那些与过早记忆和学习能力下降有关的机制。在易受年龄影响的大脑区域受损的突触可塑性被发现是最好的预测认知能力下降的老化。直到最近，关于人类神经元可塑性的推论只能从间接的可塑性测量中得出，比如认知功能的变化。然而，最近非侵入性脑刺激技术的发展，提供了多种研究工具，可以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，通过这些脑刺激技术评估的突触可塑性与脑功能相关的功能变化有着显著的联系。使用这些创新的大脑刺激技术的主要兴趣之一在于它们已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。

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.