Cellular and Molecular Mechanisms of Motor Skill Learning

学习新的运动序列的能力是人类和动物适应运动行为的基础。这种程序性能力是通过将最初不同的动作整合成一个特定的行为单元而建立起来的。这些行动的执行取决于我们对环境的了解，在编码行动-结果关系时，以及有效执行行动的能力。在动作优化过程中，初始阶段性能快速增长，随着性能渐近水平的提高，性能缓慢增长。这种优化行动的过程可能会改变行动的性质，经过广泛的练习，行动可能会成为自动或习惯性的，而不是目标导向的。在过去的十年中，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焦点。然而，对于熟练的运动是如何在细胞和分子水平上在大脑中编码的，人们知之甚少。我的研究项目的主要目标是了解在啮齿动物习得新运动任务过程中调节运动学习不同阶段的细胞和分子底物的组织和功能。我们将特别关注纹状体间接通路神经元和纹状体直接通路神经元的输入和各自在基底神经节回路中的位置所引起的可塑性之间可能存在的差异。我们将首先描述运动学习引起的结构可塑性，特别是在小鼠纹状体结构中。然后，我们将研究在运动任务学习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。理解分子过程和适应性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的功能子区域，这些区域对于特定形式的学习和动作控制是必要的，并建立皮质纹状体突触的细胞内信号通路的启发式模型，这些信号通路涉及复杂运动技能的短期和长期习得。

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.