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: 10063566
• 负责人: Henry Yin
• 金额: $ 34.78万
• 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 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10063566
• 关键词: 3-Dimensional; Anatomy; Basal Ganglia; Behavior; Behavioral; Cell Nucleus; Clinical; Code; Collection; Corpus striatum structure; Data; Disease; Dopamine; Functional disorder; Gases; Goals; Huntington Disease; Lead; Light; Mental disorders; Midbrain structure; Modeling; Motion; Motivation; Movement; Mus; Neurons; Obsessive-Compulsive Disorder; Operant Conditioning; Output; Parkinson Disease; Pathway interactions; Physiology; Population; Positioning Attribute; Procedures; Psychological reinforcement; Research; Rewards; Role; Shapes; Signal Transduction; Specific qualifier value; Structure; Substantia nigra structure; Symptoms; System; Testing; Wireless Technology; Work; addiction; autism spectrum disorder; base; behavioral outcome; diencephalon; dopaminergic neuron; in vivo; kinematics; motivated behavior; motor control; mouse model; nervous system disorder; neuromechanism; novel; optogenetics; programs; rate of change; recruit; relating to nervous system; reward expectancy; therapeutic development; tool; treatment strategy

The basal ganglia (BG) are a collection of subcortical nuclei critical for voluntary behavior. Dysfunctions in the BG circuit are found in many disorders, such as Parkinson's disease Huntington's disease, obsessive-compulsive disorder, and addiction. A better understanding of the mechanisms is critical for therapeutic developments for these disorders. Despite significant progress in our understanding of the anatomy and physiology of the BG, their contributions to voluntary behavior remain poorly understood. This proposal aims to determine how BG outputs initiate actions. Preliminary results showed a critical role of the BG circuits in controlling movement kinematics: striatal output reflects movement velocity, which is integrated by the substantia nigra pars reticulata to generate instantaneous position commands to downstream structures in the midbrain and diencephalon, nigrostriatal dopaminergic signaling, on the other hand, modulates the rate of transitions between body configurations, i.e., movement velocity. Thus single unit activity in the BG can be used to quantitatively predict the actual trajectory of any voluntary movement. This proposal aims to elucidate the computational functions of specific components of the BG circuit, and how this circuit can be recruited in motivated behavior directed towards rewards. An integrative approach will be employed, combining 1) a novel motion tracking program that provides unprecedented quantitative data on movement parameters in freely moving mice; 2) wireless in vivo recording from many single neurons in the BG during behavior; 3) optogenetic manipulation of defined BG neuronal populations. These tools will be used to determine the neural code used by the BG circuits in controlling voluntary behavior, and shed light on how rewards and motivational states can modulate behavioral vigor.

基底神经节 (BG) 是对自主行为​​至关重要的皮质下核团的集合。 许多疾病都存在 BG 回路功能障碍，例如帕金森病 亨廷顿舞蹈症、强迫症和成瘾。更好地理解 这些机制对于这些疾病的治疗发展至关重要。尽管显着 我们对 BG 解剖学和生理学的理解取得了进展，它们对 自愿行为仍然知之甚少。该提案旨在确定BG如何输出 发起行动。初步结果表明 BG 电路在控制中发挥着关键作用 运动运动学：纹状体输出反映运动速度，由 黑质网状部向下游产生瞬时位置命令 另一方面，中脑和间脑的结构，黑质纹状体多巴胺能信号传导 手，调节身体形态之间的转换速率，即运动 速度。因此，BG 中的单个单位活动可用于定量预测实际的 任何自愿运动的轨迹。该提案旨在阐明计算 BG 电路特定组件的功能，以及如何在 动机行为指向奖励。将采用综合方法， 结合 1) 一种新颖的运动跟踪程序，可提供前所未有的定量数据 自由移动小鼠的运动参数； 2）多单无线活体录音 行为期间 BG 中的神经元； 3) 确定的 BG 神经元的光遗传学操作 人口。这些工具将用于确定 BG 电路使用的神经代码 控制自愿行为，并阐明奖励和动机状态如何 调节行为活力。