Motor Sequence Learning in Basal Ganglia

流畅、看似毫不费力地完成一系列动作是日常运动的普遍特征 skills.其重要性的充分证据来自于常见的人类神经病理学（帕金森氏症 疾病，特别是），其中顺序技能特别受损。长期的运动排序技能是 最有可能的是，在多个时间尺度上，在大脑的联想、前运动和运动回路中形成。最近 有证据表明，对于这些大脑回路中的每一个，通过基底神经节（BG）的皮层下回路 选择性地促进丘脑-皮层可塑性的突触驱动调制。这些发现导致 假设BG环在序列信息的获取中发挥核心作用，但不太重要 在回忆或使用已经学习过的序列。本提案的具体目标（SA）将检验这一总体目标。 通过使用非人类灵长类动物的假设：1）确定苍白球内（GPi， 骨骼运动功能的主要BG输出核）优先编码新期间的序列信息。 学习;以及2）测试完整的BG电路是否是新序列学习所必需的。结合循环 通过BG可以在快速获得灵活的目标导向的序列表示中发挥更大的作用 虽然前运动和运动回路可能介导习惯样效应器特异性的缓慢获取， 表示。我们将通过刺激不同的皮层神经元来推断单个GPi神经元的电路成员资格。 观察顺向抑制效应。动物将执行离散序列生产任务 使用新的、熟悉的和过度训练的序列。SAl将测试序列特异性的神经元编码 GPi的关联、前运动和运动回路中的信息反映了这些回路在以下方面的预测作用： 学习新的、熟悉的和过度训练的序列。SA 2将确定BG输出的中断（即，GPI 失活或损伤）选择性地损害序列性能中与训练相关的改善。的 预测是，在关联BG回路中的失活或病变将损害新序列学习， 运动前区和运动回路的损伤将阻碍运动能力的进一步完善和固化。 熟悉的序列。这些实验的结果将有助于理解 相关性（参见说明）： 所提出的工作是理解实践导致的机制问题的核心， 在面对衰老、神经退化、中风或脑损伤时，人类运动系统的重组。 了解这些机制对旨在保留功能的治疗设计有影响， 开发补偿器运动，并最终开发新的电机容量。

The fluid, seemingly effortless execution of sequences of movements is a ubiquitous feature of everyday motor skills. Ample evidence for their importance comes from the common human neuropathologies (Parkinson's disease, in particular) in which sequential skills are especially impaired. Long-term motor sequencing skills are formed, most likely, across multiple time scales in associative, premotor, and motor circuits of the brain. Recent evidence suggests that for each of these brain circuits, a sub-cortical loop through the basal ganglia (BG) contributes selectively to reinforcement-driven modulation of thalamo-cortical plasticity. These findings lead to the hypothesis that BG loops play central roles in the acquisition of sequence information, but are less important in the recall or use of already-learned sequences. The specific aims (SAs) of this proposal will test that general hypothesis by using non-human primates: 1) to determine if neurons in the globus pallidus interna (GPi, the primary BG output nucleus for skeletomotor function) preferentially encode sequence information during new learning; and 2) to test whether intact BG circuits are necessary for new sequence learning. Associative loops through the BG may play a greater role in the fast acquisition of flexible goal-directed representations of sequence information while the premotor and motor loops may mediate slow acquisition of habit-like effector-specific representations. We will infer the circuit membership of individual GPi neurons by stimulating different cortical areas and observing the orthodromic inhibitory effects. Animals will perform a discrete sequence production task using novel, familiar and over-trained sequences. SAl will test if neuronal encoding of sequence-specific information in associative, premotor, and motor circuits of GPi reflects the predicted roles of these circuits in learning novel, familiar, and over-trained sequences. SA2 will determine if an interruption of BG output (i.e., GPi inactivation or lesion) selectively impairs training-related improvements in sequence performance. The prediction is that inactivations or lesions in the associative BG circuit will impair novel sequence learning whereas lesions in premotor and motor circuits will block the further refinement and solidification of performance of already-familiar sequences. Results from these experiments will aid in understanding the physiological basis for RELEVANCE (See instructions): TThe proposed work is central to the problem of understanding the mechansims where practice leads to to reorganization of the human motor system in the face of aging, neurodeneration, stroke or brain injury. Understanding these mechansims has an impact on the design of therapies directed at preserving function, developing compensator movements and ultimately, developing novel motor capacity.