The Role of Opponent Basal Ganglia Outputs in Behavior

基底节(BG)是对自愿行为至关重要的皮质下核团的集合。 在许多疾病中都会发现BG环路功能障碍，如帕金森氏症 亨廷顿氏症、强迫症和毒瘾。更好地理解 这些机制对这些疾病的治疗发展至关重要。尽管意义重大 我们对BG的解剖学和生理学的了解的进展，它们对 人们对自愿行为仍然知之甚少。这项提案旨在确定英国天然气集团如何产出 开始行动。初步结果显示BG回路在控制 运动运动学：纹状体输出反映运动速度，运动速度由 黑质网状部向下游发出瞬时位置指令 中脑和间脑的结构，黑质纹状体的多巴胺能信号 手，调节身体构型之间的转换速度，即运动 速度。因此，BG中的单个单位活度可以用来定量预测实际 任何自愿运动的轨迹。这项提议旨在阐明计算的 BG电路的特定组件的功能，以及如何在 以奖励为导向的动机行为。将采用综合方法， 结合1)一个新的运动跟踪程序，提供前所未有的定量数据 自由活动小鼠的运动参数；2)多个单次无线活体记录 行为过程中BG中的神经元；3)明确的BG神经元的光遗传操作 人口。这些工具将用于确定中BG电路使用的神经代码 控制自愿行为，并阐明奖励和激励状态如何 调节行为活力。

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.