The Role of Opponent Basal Ganglia Outputs in Behavior

基底神经节（BG）是一组对自主行为至关重要的皮质下核团。 BG回路的功能障碍存在于许多疾病中，例如帕金森病 亨廷顿舞蹈症、强迫症和成瘾。更好地了解 这些机制对于这些疾病的治疗发展至关重要。尽管取得了重大 我们对BG的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。本提案旨在确定BG如何输出 发起行动。初步结果表明，BG电路在控制 运动运动学：纹状体输出反映运动速度，这是由整合 黑质网状部，以产生瞬时位置命令， 中脑和间脑的结构，黑质纹状体多巴胺能信号，另一方面， 一方面，调节身体形态之间的转换速率，即，运动 速度因此，BG中的单个单位活性可用于定量预测实际的 任何自主运动的轨迹。该建议旨在阐明计算 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。将采用综合办法， 结合1）一个新的运动跟踪程序，提供前所未有的定量数据， 自由移动小鼠的运动参数; 2）来自许多单个 3）光遗传学操作限定的BG神经元 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。

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.