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.

项目摘要老实说，比赛点上的双重故障令人失望。但是这也是一个可以帮助的性能错误改善您的未来服务。 “边缘”结构，例如外侧Habenula（LHB），腹侧颗粒（VP）和腹侧对盖区域（VTA）与享乐功能相关。但这种强调可能由行为主义的传统造成的，这些传统以奖励和惩罚训练实验室动物。更通用的功能边缘系统的可能是对任何预测错误施加价，包括在运动性能。如果是这种情况，那么关于大脑处理如何奖励的数十年进步概括诸如语音，运动和音乐表演之类的运动序列任务。在过去的工作中，我们发现雄性鸣禽出乎意料地唱着正确的音符时，其VTA多巴胺（DA）神经元就是与第三个灵长类动物意外接收果汁一样激活。然后是歌曲错误，它当灵长类动物经历令人失望的奖励遗漏时，da神经元被抑制。我们还发现当男性向女性唱歌时，这些表现评估信号被关闭，而DA神经元则是被女性呼叫激活。这些发现对动机的运动学习电路具有重要意义拟议的工作。为了确定如何在VTA上游的电路中评估性能质量，我们将解剖学上识别对VTA的输入，执行损伤以测试歌曲学习所必需的，记录VTA 对微刺激不同输入的响应，并进行神经记录以确定听觉错误和/或定时信号对于错误计算很重要（AIM 1）。第二，在过去的工作中，我们将副总裁确定为唱歌过程中的听觉，电机和错误处理。在试点实验中，我们正在识别LHB和丘脑下核（STN）作为VP的新型靶标，也投射给VTA。为了剖析副总裁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Motor Cortex-Projecting VP 唱歌期间神经元（AIM 2）。最后，我们过去的发现，当男性唱歌时，da错误信号被关闭对女性来说是前所未有的。为了确定DA信号门控在行为上是否相关，我们首先测试男性是否可以从实验控制的错误中吸取了存在的女性（AIM 3.1）。测试错误信号是否已门控在全球范围内，我们将在VTA项目（听觉皮层，VP，STN，LHB）中记录神经元感知错误和女性存在（目标3.2）。总之，这些研究将确定构建运动序列的内部评估系统。理解病理的主要障碍在BG相关疾病中观察到的活动模式是对通过该信号传播的有限理解健康电路。拟议的工作旨在了解DA-BG信号的功能及其如何在电路的成功阶段进行处理。在这个问题上危在旦夕的是调整疗法的潜力，例如基于详细知识正常的脑生理。