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

基本信息

批准号：
10658875
负责人：
Jesse Heymann Goldberg
金额：
$ 36.9万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-15 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10658875
关键词：
Anatomy Animals Area Auditory Auditory area Basal Ganglia Basal Ganglia Diseases Behavior Behavioral Benchmarking Biological Models Birds Brain Cell Nucleus Complex Data Deep Brain Stimulation Disease Dopamine Emotional Ensure Evaluation Exhibits Female Future Globus Pallidus Grant Habenula Human Juice Knowledge Lateral Learning Lesion Limbic System Mammals Methods Motivation Motor Motor Cortex Movement Disorders Music Neurons Outcome Output Pathologic Pathway interactions Pattern Performance Physiology Population Primates Process Punishment Research Rewards Role Route Self-Examination Signal Transduction Songbirds Speech Sports Structure Structure of subthalamic nucleus System Testing Ventral Tegmental Area Vertebrates Work cholinergic cholinergic neuron dopaminergic neuron experience experimental study hedonic improved individualized medicine innovation instrument laboratory experience male microstimulation motor control motor learning neural neural circuit neural correlate neuromechanism novel outcome prediction response sequence learning

项目摘要

PROJECT SUMMARY Double faulting on match point is intensely disappointing. Yet it is also a performance error that could help improve your future serve. ‘Limbic’ structures such as the lateral habenula (LHb), ventral pallidum (VP) and ventral tegmental area (VTA) have classically been associated with hedonic functions. But this emphasis might result from behaviorist traditions that train lab animals with rewards and punishments. A more general function of the limbic system may be to impose valence on any prediction error, including mistakes that occur during motor performance. If this is the case, then decades of progress on how the brain processes reward can generalize to motor sequence tasks such as speech, sport, and musical performance. In past work, we discovered that when a male songbird unexpectedly sings the right note, its VTA dopamine (DA) neurons are activated in the same way as when a thirsty primate unexpectedly receives juice. And following song errors, its DA neurons are suppressed as when a primate experiences disappointing reward omission. We also found that when males sing to females, these performance evaluation signals are turned off and DA neurons are instead activated by female calls. These discoveries have important implications for motor learning circuits that motivate the proposed work. Frist, to determine how performance quality is evaluated in circuits upstream of VTA, we will anatomically identify inputs to VTA, perform lesions to test which are necessary for song learning, record VTA responses to microstimulation of distinct inputs, and conduct neural recordings to identify auditory error and/or timing signals important for error computation (Aim 1). Second, in past work we identified the VP as a hub for auditory, motor, and error processing during singing. In pilot experiments we are identifying LHb and subthalamic nucleus (STN) as novel targets of VP that also project to VTA. To dissect VP’s role in performance evaluation, we will anatomically define VP inputs and outputs, and will record STN-, LHb-, and motor cortex-projecting VP neurons during singing (Aim 2). Finally, our past discovery that DA error signals are turned off when males sing to females is unprecedented. To determine if DA signal gating is behaviorally relevant, we first test if males can learn from experimentally controlled errors with females present (Aim 3.1). To test if error signals are gated off globally, we will record neurons in VTA-projecting areas (auditory cortex, VP, STN, LHb) as we control both perceived error and female presence (Aim 3.2). Altogether, these studies will identify the neural correlates of the internal evaluation systems 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.

项目概要赛点上的双误令人非常失望，但这也是一个可能有所帮助的表现错误。改善你未来的发球能力，例如外侧缰核 (LHb)、腹侧苍白球 (VP) 和腹侧被盖区（VTA）传统上与享乐功能相关，但这种强调可能。行为主义传统的结果，通过奖励和惩罚来训练实验动物，具有更普遍的功能。边缘系统的功能可能是对任何预测错误施加效价，包括在预测过程中发生的错误如果是这样的话，那么几十年来在大脑如何处理奖励方面取得的进展可以在过去的工作中，我们将其推广到运动序列任务，例如言语、运动和音乐表演。发现当雄性鸣禽意外地唱出正确的音符时，它的 VTA 多巴胺 (DA) 神经元就像口渴的灵长类动物意外收到果汁时一样，在歌曲错误之后，它会被激活。当灵长类动物经历令人失望的奖励遗漏时，DA 神经元就会受到抑制。当雄性向雌性唱歌时，这些表现评估信号会被关闭，而 DA 神经元会被关闭。这些发现对激励运动学习回路具有重要意义。首先，为了确定如何评估 VTA 上游电路的性能质量，我们将解剖学上识别 VTA 的输入，执行损伤以测试歌曲学习所需的内容，记录 VTA 对不同输入的微刺激做出反应，并进行神经记录以识别听觉错误和/或时序信号对于误差计算很重要（目标 1）。其次，在过去的工作中，我们将 VP 确定为一个中心。在试点实验中，我们正在识别 LHb 和底丘脑。核（STN）作为 VP 的新目标，也投射到 VTA 来剖析 VP 在绩效评估中的作用，我们将在解剖学上定义 VP 输入和输出，并记录 STN-、LHb- 和运动皮层投射 VP 最后，我们过去的发现是，雄性唱歌时 DA 错误信号会关闭。为了确定 DA 信号门控是否与行为相关，我们首先测试男性是否可以。从有女性存在的实验控制错误中学习（目标 3.1）。在全球范围内，我们将记录 VTA 投射区域（听觉皮层、VP、STN、LHb）中的神经元，因为我们控制着这两个区域总而言之，这些研究将确定感知错误和女性存在的神经相关性。构建运动序列的内部评估系统是理解病理学的主要障碍。在 BG 相关疾病中观察到的活动模式是对信号通过拟议的工作旨在了解 DA-BG 信号的功能以及它们的作用。在电路的连续阶段进行处理，这个问题的关键是定制疗法的潜力，例如基于详细知识的神经回路重新编程和深部脑刺激治疗运动障碍正常的大脑生理学。