Motor Sequence Learning in Basal Ganglia

流畅的、看似毫不费力的动作序列的执行是日常运动的一个普遍特征 技能。它们的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)顺序技能特别受损的疾病。长期的运动测序技能是 很可能是在大脑的联想、运动前和运动回路中跨越多个时间尺度形成的。近期 有证据表明，对于这些大脑回路中的每一个，都有一个穿过基底节(BG)的皮质下环。 选择性地促进强化驱动的丘脑皮质可塑性的调节。这些发现导致了 假设BG环在序列信息的获取中起核心作用，但不太重要 在回忆或使用已经学到的序列时。这项提案的具体目标(SA)将考验这一总体 通过使用非人类灵长类动物的假说：1)确定苍白球内侧区(GPI， 初级BG用于骨骼运动功能的输出核)在新的 学习；以及2)测试完整的BG回路是否对新序列学习是必要的。关联循环 通过BG可能在快速习得灵活的目标导向的序列表征中起到更大的作用 信息，而运动前和运动环路可能调节习惯样效应器特异性的缓慢获得 申述。我们将通过刺激不同的大脑皮层来推断单个GPI神经元的回路成员 并观察顺行抑制效应。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将测试神经元编码是否具有序列特异性 GPI的关联、前置马达和马达回路中的信息反映了这些回路在 学习新奇的、熟悉的和过度训练的序列。SA2将确定BG输出(即GPI)的中断 失活或损伤)选择性地损害与训练相关的序列性能的改善。这个 预测是，相关BG回路中的失活或损伤将损害新的序列学习，而 前置马达和马达电路中的损伤将阻碍性能的进一步细化和固化 已经很熟悉的序列。这些实验的结果将有助于理解 相关性(请参阅说明)： 拟议的工作是理解机制的核心问题，实践导致 面对衰老、神经再生、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护功能的疗法的设计有影响， 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.