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（由适用提供）：NINDS的原理是确定神经系统如何构建运动序列。运动序列学习需要多巴胺（DA） - 基质神经节（BG）电路，但目前尚不清楚这些电路如何指导试验和错误的学习过程。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动（例如食物或果汁）的研究。然而，帕金森氏症，亨廷顿和肌张力障碍等BG疾病的症状包括降解与寻求奖励无关的运动行为。大多数人类的行为，例如学习运动或乐器，不是追求外部奖励的简单动作，而是通过将性能与内部目标相匹配而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，可以研究内部引导运动序列的构建方式。 Zebra通过将复杂的人声序列与导师的歌曲的听觉记忆相匹配，从而学习了他们的歌。这种感觉运动学习需要一个DA-BG电路，该电路属于“歌曲系统”的一部分。我们将把核心优势应用于醒着的电生理学，以解读可在练习过程中评估运动性能的方法。首先，为了测试DA神经元是否评估了运动性能（学习的“误差”部分），我们将在使用扭曲的听觉反馈（AIM 1）控制歌曲“错误”时进行BG射击DA神经元的第一个录音。初步记录支持DA神经元在唱歌过程中编码“性能预测错误”信号的假设。为了确定上游感觉运动信号如何计算“错误”，我们将在错误反馈任务期间从听觉皮质和BG项目记录到唱歌鸟类的DA神经元（AIM 2）。最后，斑马在两个依赖于DA的电机状态下罚款：单独的练习模式和一个女性定向的，定型的性能模式。为了测试DA是否可以评估性能并控制其变异性，我们将在未向导的歌曲状态过渡期间记录DA神经元（AIM 3）。总之，这些研究将确定构建运动序列的内部评估系统的神经元相关。了解与BG相关疾病中观察到的病理活性模式的主要障碍是通过健康回路对信号传播的有限理解。拟议的工作旨在了解DA-BG信号的功能以及如何在电路阶段进行处理。在这个问题上，基于对正常脑生理学的详细知识，在此问题上危及了量身定制疗法，例如神经回路重新编程和对运动障碍的深度刺激。