Experience-dependent Compensation and Brain Plasticity

获得新的运动技能关键取决于经验和练习。依赖经验的运动技能学习代表了大脑损伤患者克服运动功能丧失的一种中央机制。随着时间的推移，大多数脑损伤患者都需要学习某种代偿性运动策略，以取代失去的运动能力。我的NSERC资助的工作表明，代偿性运动策略是明显可识别的，并与原始的、完整的运动区分开来，它们密切地反映了潜在神经路径的解剖重新安排。值得注意的是，我们发现个体在补偿策略的使用上有相当大的差异。薪酬的个体差异似乎受到年龄、性别和压力等内在因素的影响，但也受到环境条件、经历类型和培训的影响。因此，我假设，年龄、性别、压力等内在因素，以及环境条件和经历等外在因素，对补偿和大脑可塑性有重要作用。我认为补偿策略的个体差异可以作为研究大脑可塑性的基本机制的模型。我的研究旨在使用补偿作为一个模型来研究内在因素和经验如何与大脑可塑性的基本神经元和分子机制相互作用。 在拟议的研究中，我们将在实验室大鼠和人类受试者中确定补偿策略及其神经元和分子基础：(1)调查熟练运动中的运动学习和补偿策略如何适应与生理、遗传和表观遗传变量有关的任务特定需求；(2)确定作为年龄、性别和应激反应函数的运动技能获得和补偿策略；(3)确定环境经验如何促进或阻碍运动学习和补偿；以及(4)检查前几代人的经验是否产生可遗传的补偿和大脑可塑性模式。在大鼠和人类受试者身上使用创新技术，我们将识别运动学习、补偿和大脑可塑性的依赖于活动的生理、遗传和表观遗传调节。我们现在有了现代的、活体的、高分辨率的工具，可以对动态大脑可塑性和行为进行新的纵向研究。我预测补偿可以作为一个极好的模型来研究“先天与后天”对大脑可塑性的影响。 本文提出的研究补偿的新的多学科研究方法将极大地促进对大脑可塑性的神经生物学机制和经验依赖性调节的理解。由于病变脑中的补偿与促进发育和衰老的神经机制相同，因此对补偿的研究可以在更一般的水平上深入了解神经系统的功能。因此，了解代偿的神经基础是基础神经科学的核心问题。这项研究最终也将对当前的技术趋势产生影响；例如，我的实验室已经开始开发新技术，使用生物工程便携式健康设备来量化大脑可塑性的分子调节器。

The acquisition of new motor skills critically depends on experience and practice. Experience-dependent motor skill learning represents a central mechanism by which individuals with a brain lesion overcome loss of motor function. Most individuals with a brain lesion are required to learn some kind of compensatory movement strategies over time that substitute for lost motor capacity. My NSERC-funded work showed that compensatory movement strategies are clearly recognizable and distinguishable from original, intact movements, and they closely reflect anatomical rearrangements of the underlying neuronal pathways. Notably, we found a considerable variation in the use of compensatory strategies among individuals. Individual variation in compensation appears to be influenced by intrinsic factors such as age, sex and stress, but is also determined by environmental conditions, the type of experience and training. Thus, I hypothesize that intrinsic factors such as age, sex, stress, and extrinsic factors, such as environmental conditions and experiences, contribute in important ways to compensation and brain plasticity. I propose that individual variations in compensatory strategies can be used as a model to study the fundamental mechanisms of brain plasticity. My research is directed toward using compensation as a model to study how intrinsic factors and experiences interact with the fundamental neuronal and molecular mechanisms of brain plasticity. In the proposed research, we will identify compensatory strategies and its neuronal and molecular basis in laboratory rats and human subjects (1) to investigate how motor learning and compensatory strategies in skilled movements adapt to task-specific demands in relation to physiological, genetic and epigenetic variables; (2) to identify strategies in motor skill acquisition and compensation as a function of age, sex and stress response; (3) to determine how environmental experiences can facilitate or impede motor learning and compensation; and (4) to examine if experience in previous generations generates heritable patterns of compensation and brain plasticity. Using innovative technologies in rats and human subjects, we will identify activity-dependent physiological, genetic and epigenetic regulators of motor learning, compensation and brain plasticity. We now have modern, in vivo, high-resolution tools available to pursue novel longitudinal studies of dynamic brain plasticity and behaviour. I predict that compensation can be used as a superb model to study the influences of “nature versus nurture” on brain plasticity. The novel, multidisciplinary research approach to the study of compensation proposed here will significantly advance the understanding of neurobiological mechanisms and experience-dependent regulation of brain plasticity. Because compensation in the lesion brain is mediated by the same neural mechanisms as those that contribute to development and aging, the study of compensation leads to insights into nervous system function on a more general level. Thus, understanding the neural basis of compensation represents a problem that is central to basic neuroscience. This research will also ultimately have an impact on current technology trends; for example, my laboratory has already started to generate new technologies to quantify molecular regulators of brain plasticity using bioengineered portable health devices.