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: 10531242
• 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/10531242
• 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; 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; behavior measurement; experimental study; imaging modality; in vivo calcium imaging; innovation; kinematics; motivated behavior; motor control; mouse model; neglect; nervous system disorder; neural; novel; optogenetics; rate of change; 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 虽然基底神经节（BG）长期以来一直与动作选择有关，但特异性 电路机制仍然知之甚少。根据传统模式， 抑制BG输出是通过去抑制打开门以选择特定动作。最近的工作， 然而，他对这一模型提出了质疑，他证明了BG的输出远比 最初假设。通过测量连续的行为指标和神经活动 同时，最近的研究表明，血糖输出有多种功能类别， 神经元代表动作的不同向量分量。特别是纹状体输出 神经元被证明编码运动速度，而黑质输出神经元代表 瞬时位置坐标这些结果表明，BG电路包含一个神经 其输出可以精确地指定动作的详细空间和时间特征的集成器 并且持续地。这些结果提示了一种新的模型，其中直接（纹状体黑质）和间接 （纹状体）通路一起工作，定量地塑造动作命令。这项建议 旨在阐明这些途径如何促进小鼠的动机行为。是 假设直接和间接途径实现特定的计算功能： 尽管直接通路输出决定神经积分器输出的变化率， 间接通路释放积分器。为了验证这一假设，我们将使用体内钙 成像以测量感觉运动神经元中的直接和间接通路神经元中的神经活动 纹状体在奖赏引导行为中的单神经元分辨。我们还将使用光遗传学 选择性地操纵这些通路中的活动，以确定它们的因果关系， 贡献的行为，并确定如何多巴胺可以调节他们的活动， 行为老鼠最后，我们将研究直接和间接之间的功能相互作用。 通过反复抑制途径。从拟议的实验结果将有显着 对理解和治疗涉及BG的各种疾病的意义。