Circuit mechanisms of value-based decision making in the basal ganglia

 描述(由申请人提供)：基底神经节功能障碍与多种神经和精神障碍的运动和认知障碍有关，包括帕金森氏症、强迫症和注意力缺陷障碍。基底节由两个主要回路组成，即直接通路和间接通路，它们被认为对运动具有相反的影响。虽然之前的许多研究考察了这些回路中的活动平衡是如何影响运动控制的，但对于它们对更高认知功能的贡献，人们知之甚少。最近的研究强调了基底节在强化学习和决策中的中心作用，并提出决策过程中的功能障碍可能是基底节疾病中观察到的一些认知缺陷的基础。进展的最大障碍之一是，直接和间接通路投射神经元混合在一起，电生理上无法区分，这使得研究这些回路在动物行为中的功能作用变得极其困难。随着光遗传学的发展，光激活离子通道可以针对遗传定义的神经元群体，从而使在行为动物中剖析这些电路的功能成为可能。我们的目标是通过应用先进的光学和电生理方法来确定基底神经节中决策和强化学习的特定路径机制。最近使用这些工具的研究表明，直接路径在强化学习中起选择作用，间接路径在惩罚学习中起作用。这可能对毒瘾和抑郁症有深远的影响，因为从积极和消极的结果中学习的选择性缺陷可能是与这些障碍相关的一些症状的基础。我们将在这项工作的基础上，研究特定路径的神经元活动和可塑性如何在动态决策任务中发挥学习作用。通过我们的发现，我们希望进一步了解强化学习背后的基本回路机制，并阐明在基底节疾病中观察到的更高的认知缺陷。

 DESCRIPTION (provided by applicant): Dysfunction of the basal ganglia has been associated with motor and cognitive deficits across a wide range of neurological and psychiatric disorders, including Parkinson's disease, obsessive compulsive disorder, and attention deficit disorder. The basal ganglia comprise two major circuits, the direct and indirect pathways, which are thought to have opposing effects on movement. While many previous studies examined how the balance of activity in these circuits shapes motor control, relatively little is known about their contributions to higher cognitive function. Recent work highlighted the basal ganglia's central role in reinforcement learning and decision-making and suggested that dysfunction in the decision process may underlie some of the cognitive deficits that are observed in basal ganglia disorders. One of the greatest barriers to progress is the fact that the direct and indirect pathwa projection neurons are intermingled and electrophysiologically indistinguishable, making it extremely difficult to study the functional role of these circuits in behaving animals. With the development of optogenetics, light-activated ion channels can be targeted to genetically defined neuronal populations, making it feasible to dissect the function of these circuits in behaving animals. Our goal is to define the pathway-specific mechanisms of decision making and reinforcement learning in the basal ganglia by applying advanced optical and electrophysiological methods. Recent studies using these tools revealed that the direct pathway plays a selective role in learning from reinforcement, and the indirect pathway plays a role in learning from punishment. This may have profound implications for drug addiction and depression, since selective deficits in learning from positive and negative outcomes may underlie some of the symptoms associated with these disorders. We will build on this work by investigating how pathway-specific neuronal activity and plasticity plays a role in learning in a dynamic decision-making task. With our findings we hope to further understand the basic circuit mechanisms underlying reinforcement learning, and to shed light on the higher cognitive deficits observed in basal ganglia disorders.