Motor sequences and basal ganglia-cortical circuits

运动序列和基底神经节皮质回路

• 批准号: 10532192
• 负责人: ROBERT STERLING TURNER
• 金额: $ 34.23万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10532192
• 关键词: Anatomy; Animals; Area; Automobile Driving; Back; Basal Ganglia; Behavior; Behavioral; Bilateral; Brain; Brain region; Cell Nucleus; Clinical; Crystallization; Dimensions; Disease; Dystonia; Electrodes; Familiarity; Functional disorder; Ganglia; Globus Pallidus; Goals; Habits; Human; Impairment; Individual; Interruption; Lead; Learning; Lesion; Limb structure; Link; Liquid substance; Mediating; Memory; Methods; Monkeys; Motor; Motor Cortex; Motor Skills; Movement; Neurons; Output; Parkinson Disease; Pathologic; Performance; Physiological; Play; Production; Psychological reinforcement; Response to stimulus physiology; Role; Sampling; Site; Symptoms; Task Performances; Testing; Time; Training; density; experimental study; flexibility; human disease; improved; motor behavior; motor learning; nervous system disorder; neural; nonhuman primate; novel; pharmacologic; preference; prevent; response; segregation; sequence learning; skills; theories; transmission process

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.

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 行为这种能力的重要性的充分证据来自于人类常见的疾病 （尤其是帕金森氏病），其中顺序技能特别受损。长期电动机 排序技能很可能是通过平行皮层-次皮层回路的合作形成的 涉及大脑的联想、前运动和运动区域。最近的证据表明，对于其中的每一个 在大脑回路中，通过基底神经节（BG）的皮层下回路选择性地促进了脑电驱动的 调节丘脑-皮质可塑性，而皮质非常适合作为长期保留和有效的 熟练技能的回忆。这些发现导致了这样的假设，即BG环在糖尿病的发生中起着核心作用。 获取序列信息，而解剖学连接的皮层区域对于 存储和使用已学习的信息。本提案的具体目标（SA）将检验这一总体目标。 （1）为了确定苍白球内（GPi，a 初级BG输出核）在学习和产生过程中优先编码序列任务信息 最近学习的序列。皮质神经元被预测不会表现出对最近学习的偏好。 序列的(2)为了测试完整的BG电路是否主要用于学习和产生最近的- 学习序列。相比之下，皮质回路被认为是必要的，即使是对学习良好的序列。 通过皮层和BG的关联回路可能在目标的快速获得和灵活回忆中发挥更大的作用， 有向序列信息运动前区和运动环路可能介导习惯性行为的缓慢获得 特定于效应器的表示。我们将通过刺激单个GPi神经元来推断其电路成员 不同皮层区的神经元，观察顺向抑制效应。动物们会表演一个不连续的序列 生产任务在随机的，从新奇到熟悉的和过度训练的序列之间交替。SA 1将 测试在联想、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 这些电路的BG和皮质成分的不同作用。SA 2将确定BG输出是否中断 (i.e., GPi失活或损伤）选择性地损害最近学习序列的学习或回忆。 相反，大脑皮层的失活也会破坏对熟悉序列的回忆。结果 从这些实验中将有助于理解正常和受损的顺序的生理基础， 人类的行为。