The Role of Opponent Basal Ganglia Outputs in Behavior

对手基底神经节输出在行为中的作用

• 批准号: 10367065
• 负责人: Henry Yin
• 金额: $ 40.25万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10367065
• 关键词: 3-Dimensional; Acceleration; Axon; Basal Ganglia; Behavior; Behavioral; Brain; Brain region; Calcium; Complex; Corpus striatum structure; Deceleration; Disease; Disinhibition; Dopamine; Event; Huntington Disease; Image; Knowledge; Lead; Light; Measures; Mental disorders; Modeling; Motion; Movement; Mus; Nature; Neurons; Obsessive-Compulsive Disorder; Organism; Output; Parkinson Disease; Pathology; Pathway interactions; Performance; Population; Positioning Attribute; Recurrence; Resolution; Rewards; Role; Shapes; Slice; Specific qualifier value; Synapses; Testing; Textbooks; Time; Work; autism spectrum disorder; base; behavior measurement; experimental study; imaging modality; in vivo calcium imaging; innovation; kinematics; motivated behavior; motor control; mouse model; neglect; nervous system disorder; novel; optogenetics; rate of change; relating to nervous system; therapeutic development; treatment strategy; vector

Project Summary Although the basal ganglia (BG) have long been implicated in action selection, the specific circuit mechanisms remain poorly understood. According to traditional models, the role of the inhibitory BG output is to open a gate to select a specific action via disinhibition. Recent work, however, has questioned this model by demonstrating that BG output is far more complex than originally assumed. By measuring continuous behavioral measures and neural activity simultaneously, recent studies showed that there are multiple functional classes of BG output neurons representing different vector components of actions. In particular, striatal output neurons were shown to encode movement velocity whereas nigral output neurons represent instantaneous position coordinates. These results suggest that BG circuits contain a neural integrator whose output can specify detailed spatial and temporal features of actions precisely and continuously. These results suggest a new model in which direct (striatonigral) and indirect (striatopallidal) pathwayswork together to quantitatively shape action commands. This proposal aims to elucidate how these pathways contribute to motivated behavior in mice. It is hypothesized that direct and indirect pathways implement specific computational functions: whereas direct pathway output determines the rate of change in the neural integrator output, the indirect pathway discharges the integrator. To test this hypothesis, we will use in vivo calcium imaging to measure neural activity in direct and indirect pathway neurons in the sensorimotor striatum with single-neuron resolution in reward-guided behavior. We will also use optogenetic to manipulate activity in these pathways selectively, in order to determine their causal contributions to behavior, and to determine how dopamine may modulate their activity in freely behaving mice. Finally, we will study functional interactions between direct and indirect pathways via recurrent inhibition. Results from proposed experiments will have significant implications for understanding and treating various disorders implicating the BG.

项目摘要 尽管基底神经节（BG）长期以来一直与作用选择有关 电路机制的理解仍然很少。根据传统模型， 抑制性BG输出是通过抑制打开门，以选择特定的动作。最近的工作， 但是，通过证明BG输出比 最初是假定的。通过测量连续的行为措施和神经活动 同时，最近的研究表明，BG输出有多种功能类别 代表动作的不同矢量成分的神经元。特别是纹状体输出 表明神经元编码运动速度，而nigral输出神经元代表 瞬时位置坐标。这些结果表明BG电路包含神经 积分器的输出可以精确指定动作的详细空间和时间特征 并且连续。这些结果表明了一个新模型，其中直接（纹状体）和间接 （纹状体）途径工作，以定量塑造动作命令。这个建议 旨在阐明这些途径如何促进小鼠的动机行为。这是 假设直接和间接途径实现特定的计算功能： 直接途径输出决定了神经积分器输出的变化速率，但 间接途径排放集成器。为了检验该假设，我们将使用体内钙 成像以测量感觉运动直接和间接途径神经元中的神经活动 纹状体具有奖励指导行为的单神经元分辨率。我们还将使用光遗传学 选择性地操纵这些途径的活动，以确定其因果关系 对行为的贡献，并确定多巴胺如何自由地调节其活性 行为小鼠。最后，我们将研究直接和间接之间的功能相互作用 通过反复抑制的途径。提出的实验的结果将具有重要的 理解和治疗各种疾病的影响。