Neural Mechanisms of Performance Evaluation During Motor Sequence Learning

项目总结 赛点上的双误令人非常失望。然而，它也是一个性能错误，这可能会有所帮助 提高你未来的发球率。边缘结构，如外侧缰核(LHb)、腹侧苍白球(Vp)和 腹侧被盖区(VTA)通常与享乐功能联系在一起。但这种强调可能会 这源于行为主义传统，即用奖惩来训练实验室动物。更一般的函数 边缘系统的价值可能是对任何预测错误施加价格，包括在 马达性能。如果是这样的话，几十年来在大脑如何处理奖励方面的进展可以 推广到运动序列任务，如演讲、运动和音乐表演。在过去的工作中，我们 发现当一只雄性鸣鸟出人意料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一样被激活。在歌曲错误之后，它的 当灵长类动物经历令人失望的奖赏缺失时，DA神经元受到抑制。我们还发现， 当雄性对雌性歌唱时，这些表现评估信号被关闭，取而代之的是DA神经元 被雌性叫声激活。这些发现对运动学习回路具有重要的意义 建议的工作。首先，为了确定如何评估VTA上游电路的性能质量，我们将 解剖识别VTA的输入，进行损伤测试，以测试歌曲学习所需的VTA，记录VTA 对不同输入的微刺激的反应，并进行神经记录以识别听觉错误和/或 定时信号对误差计算很重要(目标1)。其次，在过去的工作中，我们将副总裁确定为 歌唱过程中的听觉、运动和错误加工。在初步实验中，我们确定了LHb和丘脑下部 核团(STN)是VP的新靶点，也投射到VTA。为了剖析副总裁在绩效评估中的角色， 我们将解剖地定义VP的输入和输出，并记录STN、LHb和运动皮质投射的VP 歌唱中的神经元(目标2)。最后，我们过去的发现是，当雄性歌唱时，DA错误信号被关闭 对女性来说是前所未有的。为了确定DA信号门控是否与行为相关，我们首先测试雄性是否可以 在女性在场的情况下从实验控制的错误中学习(目标3.1)。测试错误信号是否关闭 在全球范围内，我们将记录VTA投射区域(听觉皮质、VP、STN、LHb)的神经元，因为我们控制两者 感知错误和女性存在(目标3.2)。总而言之，这些研究将确定 构建运动序列的内部评估系统。理解病理学的一个主要障碍 在BG相关疾病中观察到的活动模式是对通过 健康的赛道。拟议的工作旨在了解DA-BG信号的功能以及它们是如何 在电路的连续阶段处理。这个问题的关键是量身定做治疗方法的可能性，例如 基于详细知识的运动障碍神经回路重新编程和脑深部刺激 正常的大脑生理状态。

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.