Cellular and Molecular Mechanisms of Motor Skill Learning

学习新运动序列的能力是人类和动物生活中适应运动行为的基础。这种类型的程序能力是通过将最初不同的动作整合成一个特定的行为单位来建立的。这些行动的执行取决于我们对环境的了解、对行动-结果关系的编码以及有效执行行动的能力。在优化动作的过程中，存在一个性能快速增长的初始阶段，然后随着性能达到渐近水平而缓慢增长。这个动作的优化过程可能会改变动作的性质，经过广泛的练习，动作可能会变成自动的或习惯性的，而不是目标导向的。在过去的十年里，寻找调节运动学习的神经元底物一直是大量动物和人类研究的重点。然而，关于大脑在细胞和分子水平上如何编码熟练的运动，人们知之甚少。我的研究计划的主要目标是了解细胞和分子底物的组织和功能，这些底物在啮齿动物获得新的运动任务期间调节运动学习的不同阶段。将特别注意在纹状体苍白质间接或纹状体黑质直接通路神经元中诱导的可塑性之间可能存在的差异，这些可塑性涉及它们的输入和基底节回路中各自的位置。我们将首先描述运动学习诱导的结构可塑性，特别是在小鼠的纹状体结构中。然后，我们将研究在学习运动任务的过程中，皮质纹状体突触整合多巴胺和谷氨酸信号的细胞内机制。了解分子过程和适应行为之间的关系是神经科学研究的一个重要但艰巨的目标。我们的数据将确定纹状体中特定形式的学习和动作控制所必需的功能亚区，并建立皮质纹状体突触细胞内信号通路的启发式模型，该通路参与复杂运动技能的短期和长期获得。

The capacity to learn new motor sequences is fundamental to adaptive motor behaviour in human and animal life. This type of procedural ability builds through the integration of initially distinct movements into one particular behavioural unit. The execution of those actions depends on our knowledge of the environment, in encoding action-outcome relations, and on the capacity to execute the actions efficiently. In the process of optimizing the action, there is an initial stage of rapid increment in performance, which is followed by slow increment as performance reaches asymptotic levels. This process of optimization of the action may change the nature of the action, and after extensive practice the action may become automatic or habitual, instead of goal directed. The search for the neuronal substrates regulating motor learning has been the focus of a large body of animal and human studies in the past decade. However, little is known as to how skilled movement is encoded in the brain at the cellular and molecular levels. The major goal of my research program is to understand the organization and functions of the cellular and molecular substrates that regulates the different phases of motor learning during the acquisition of a new motor task in rodents. A particular attention will be paid to the differences that might exist between the plasticity induced in the striatopallidal indirect or striatonigral direct pathway neurons in regards to their inputs and respective places in the basal ganglia circuitry. We will first characterize motor learning-induced structural plasticity particularly in the striatum structures in mice. We will then investigate the intracellular mechanisms that integrate dopamine and glutamate signal at the corticostriatal synapses during the learning of motor tasks. Understanding the relationship between molecular processes and adaptive behaviour is an important but daunting goal of neuroscience research. Our data will identify the functional sub-regions of the striatum that are necessary for specific forms of learning and action control and establish a heuristic model of the intracellular signalling pathways of the corticostriatal synapse that are involved in the short and long-term acquisition of a complex motor skill.