Motor sequences and basal ganglia-cortical circuits

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 行为。这种能力的重要性的充分证据来自于常见的人类疾病 (尤其是帕金森氏症)顺序技能特别受损。长期马达 测序技能很可能是通过平行的皮质-皮质下回路的合作形成的 涉及大脑的关联区、运动前区和运动区。最近的证据表明，对于其中的每一个 大脑回路，通过基底节(BG)的皮质下环路选择性地参与强化驱动 丘脑皮质可塑性的调节，而皮质非常适合作为长期保持和有效的场所 回想起练就的技能。这些发现导致假设BG环在脑电活动中起核心作用。 序列信息的获取，而解剖连接的皮质区域对于 存储和使用已学到的信息。这项提案的具体目标(SA)将考验这一总体 使用非人类灵长类动物的假说：(1)确定苍白球内侧区(GPI，a)的神经元 初级BG输出核)在学习和生产过程中优先编码序列任务信息 最近学到的序列。据预测，皮质神经元不会表现出对最近学习到的知识的偏好 序列。(2)测试完整的BG电路是否主要用于学习和生产最近的- 学习序列。相比之下，大脑皮层回路被预测为必要的，即使对于学习良好的序列也是如此。 大脑皮质和大脑皮质的联想环在快速习得和灵活回忆目标--的过程中可能发挥更大的作用 定向序列信息。前置马达和马达回路电路可以调节习惯样的缓慢获得 特定于效应器的表示。我们将通过刺激来推断单个GPI神经元的回路成员 不同皮质区域，观察顺行抑制效应。动物将执行一个离散的序列 在随机的、新奇的和过度训练的序列之间以块为单位交替的生产任务。SA1将 测试联想、前运动和运动回路中任务信息的神经元编码是否反映了预测的 这些回路的BG和皮质成分的作用是不同的。SA2将确定BG输出是否中断 (例如，GPI失活或损伤)选择性地损害对最近学习的序列的学习或回忆。 相比之下，大脑皮层的失活预计也会扰乱对学习得很好的序列的回忆。结果 这些实验将有助于理解序列正常和受损的生理基础 人类的行为。

The fluid, seemingly effortless execution of sequences of movements is a ubiquitous feature of everyday motor behavior. Ample evidence for the importance of this ability comes from the common human diseases (Parkinson's disease, in particular) in which sequential skills are especially impaired. Long-term motor sequencing skills are formed, most likely, through the cooperation of parallel cortical-sub-cortical circuits involving associative, premotor, and motor regions of the brain. Recent evidence suggests that for each of these brain circuits, the sub-cortical loop through the basal ganglia (BG) contributes selectively to reinforcement-driven modulation of thalamo-cortical plasticity while cortex is well-suited as a site for long-term retention and efficient recall of well-practiced skills. These findings lead to the hypotheses that BG loops play central roles in the acquisition of sequence information whereas the anatomically-connected cortical areas are more important for the storage and use of already-learned information. 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, a primary BG output nucleus) preferentially encode sequence task information during learning and the production of recently learned sequences. Cortical neurons are predicted to not show a preference for recently learned sequences. (2) To test if intact BG circuits are necessary primarily for the learning and production of recently- learned sequences. Cortical circuits, in contrast, are predicted to be necessary even for well-learned sequences. Associative loops through cortex and BG may play greater roles in the fast acquisition and flexible recall of goal- directed sequence information. The premotor and motor loop circuits 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 alternating in blocks between random, novel-to-familiar and over-trained sequences. SA1 will test if neuronal encoding of task information in associative, premotor, and motor circuits reflects the predicted divergent roles for BG- and cortical-components of these circuits. SA2 will determine if interruptions of BG output (i.e., GPi inactivation or lesion) selectively impair the learning or recall of recently learned sequences. Inactivations of cortex, in contrast, are predicted to also disrupt the recall of well-learned sequences. Results from these experiments will aid in understanding the physiological basis for normal and impaired sequential behavior in humans.