Neural mechanisms of performance evaluation during motor sequence learning

运动序列学习过程中表现评估的神经机制

• 批准号: 9136884
• 负责人: Jesse Heymann Goldberg
• 金额: $ 33.73万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9136884
• 关键词: Affect; Animals; Auditory; Basal Ganglia; Basal Ganglia Diseases; Behavior; Benchmarking; Biological Models; Birds; Brain; Cell Nucleus; Complex; Corpus striatum structure; Deep Brain Stimulation; Disease; Dopamine; Dystonia; Electrophysiology (science); Evaluation; Exhibits; Feedback; Female; Food; Globus Pallidus; Goals; Health; Hearing; Human; Huntington Disease; Juice; Knowledge; Learning; Lesion; Mammals; Mediating; Memory; Modeling; Motor; Motor Skills; Motor output; Movement Disorders; National Institute of Neurological Disorders and Stroke; Nervous system structure; Outcome; Parkinson Disease; Pathway interactions; Pattern; Performance; Physiology; Process; Prosencephalon; Recording of previous events; Rewards; Role; Self-Examination; Sensory; Signal Transduction; Songbirds; Sports; Staging; Stereotyping; Symptoms; System; Testing; Time; Update; Vertebrates; Work; auditory feedback; awake; base; bird song; cell type; control trial; dopaminergic neuron; innovation; instrument; motor control; motor learning; neural circuit; neural correlate; neuromechanism; novel; programs; relating to nervous system; sequence learning; signal processing; tutoring; zebra finch

 DESCRIPTION (provided by applicant): A principle aim of the NINDS is to determine how motor sequences are constructed by the nervous system. Dopamine (DA)-basal ganglia (BG) circuits are required for motor sequence learning, but it remains unclear how these circuits guide the trial-and-error learning process. Remarkably, our current understanding of these pathways comes largely from studies of animals learning simple actions for external rewards such as food or juice. Yet symptoms of BG diseases such as Parkinson's, Huntington's and dystonia include degradation of motor behaviors unrelated to reward seeking. And most human behaviors, such as learning a sport or an instrument, are not simple actions in pursuit of external rewards but are instead complex motor sequences learned by matching performance to internal goals. The songbird model system offers a unique opportunity to study how internally guided motor sequences are constructed. Zebra finches learn their song by matching a complex vocal sequence to an auditory memory of a tutor song. This sensorimotor learning requires a DA-BG circuit that is part of a tractable 'song system.' We will apply our core strengths in awake- behaving electrophysiology to the tractable songbird model system to decipher how motor performance is evaluated during practice. First, to test if DA neurons evaluate motor performance (the 'error' part of learning) we will conduct the first-ever recordings of BG-projecting DA neurons while controlling song 'error' with distorted auditory feedback (Aim 1). Preliminary recordings support the hypothesis that DA neurons encode 'performance prediction error' signals during singing. To determine how upstream sensorimotor signals compute 'error,' we will record from auditory cortical and BG projections to DA neurons in singing birds during the error-feedback task (Aim 2). Finally, zebra finches sing in two DA-dependent motor states: a variable practice mode when alone and a female-directed, stereotyped performance mode. To test if DA can both evaluate performance and also control its variability, we will record DA neurons during the error feedback task during undirected-to-directed song state transitions (Aim 3). Altogether, these studies will identify the neural correlates of the internal evaluation system that construct motor sequences. A major impediment to understanding pathological activity patterns observed in BG-related diseases is a limited understanding of signal propagation through the healthy circuit. The proposed work aims to understand the functions of DA-BG signals and how they are processed at successive stages of the circuit. At stake in this issue is the potential to tailor therapies, such as neural circuit re-programming and deep brain stimulation for movement disorders, based on detailed knowledge of normal brain physiology.

 描述（由申请人提供）：NINDS 的主要目标是确定神经系统如何构建运动序列。多巴胺（DA）-基底神经节（BG）回路是运动序列学习所必需的，但目前尚不清楚这些回路如何指导试错学习过程。值得注意的是，我们目前对这些途径的理解主要来自对动物学习简单行为以获得食物或果汁等外部奖励的研究。然而，帕金森氏症、亨廷顿氏症和肌张力障碍等 BG 疾病的症状包括与奖励寻求无关的运动行为退化。大多数人类行为，例如学习一项运动或一种乐器，并不是追求外部奖励的简单行为，而是通过将表现与内部目标相匹配来学习的复杂运动序列。鸣禽模型系统提供了一个独特的机会来研究如何构建内部引导的运动序列。斑马雀通过将复杂的声音序列与导师歌曲的听觉记忆相匹配来学习歌曲。这种感觉运动学习需要 DA-BG 电路，该电路是易于处理的“歌曲系统”的一部分。我们将把我们在清醒行为电生理学方面的核心优势应用到易驯服的鸣禽模型系统中，以破译在练习过程中如何评估运动表现。首先，为了测试 DA 神经元是否评估运动表现（学习的“错误”部分），我们将首次记录 BG 投射的 DA 神经元，同时用扭曲的听觉反馈控制歌曲“错误”（目标 1）。初步记录支持这样的假设：DA 神经元在歌唱过程中编码“表演预测误差”信号。为了确定上游感觉运动信号如何计算“误差”，我们将在误差反馈任务期间记录从听觉皮层和 BG 到 DA 神经元的投射（目标 2）。最后，斑马雀以两种依赖于 DA 的运动状态歌唱：单独时的可变练习模式和女性主导的刻板表演模式。为了测试 DA 是否既可以评估性能又可以控制其变异性，我们将在非定向到定向歌曲状态转换期间的错误反馈任务期间记录 DA 神经元（目标 3）。总而言之，这些研究将确定构建运动序列的内部评估系统的神经相关性。了解 BG 相关疾病中观察到的病理活动模式的一个主要障碍是对通过健康回路的信号传播的有限了解。拟议的工作旨在了解 DA-BG 信号的功能以及它们如何在电路的连续阶段进行处理。这个问题的关键是基于对正常大脑生理学的详细了解，定制治疗方法的潜力，例如针对运动障碍的神经回路重新编程和深部脑刺激。