Learning and Selection in the Basal Ganglia

描述（由申请人提供）：基底神经节（BG）功能障碍，如帕金森病、强迫症和药物滥用，会产生许多运动和认知缺陷。然而，目前的治疗干预大多是经验性的，其潜在的机制仍然知之甚少。这反映了我们对基底神经节的不同分区如何相互作用的知识不足，因此它们的输出可以自适应地调节下游结构中神经元的活动。到目前为止，几乎所有有影响力的BG模型都提出，它们参与选择适当的行动（行动选择），并根据先前的结果改变选择不同行动的倾向（强化学习）。然而，这些功能是如何通过BG在平行的解剖学通路上实现的仍然是粗略的理解，因为只有少数生理学研究系统地比较了在旨在探索特定认知过程的行为任务期间BG不同细分的神经元的活动。本申请中提出的研究将调查分布在BG的三个主要组成部分中的信号如何有助于动作选择和强化学习。具体地说，我们将重点放在基底神经节的输出核团，即苍白球（GPi）和黑质网状部（SNr）的内段，此外， 苍白球（GPe）的外部部分，被认为对BG的所有其他成分产生实质性影响。跨BG的不同隔室的神经信号的比较对于理解基底神经节内和跨基底神经节信号处理的性质（包括直接和间接通路的作用）是必不可少的。在我们的实验中，我们将首先测试在决策任务期间，GPe和GPi/SNr中对替代行动预期结果的估计是否动态且持续更新。特别是，将测试它们是否显示出与预期成果的意外变化有关的活动增强。其次，我们还将测试与奖励和惩罚相关的信号是否在BG的不同细分中被不同地编码。这些研究的结果将为开发更有效的治疗BG功能障碍引起的许多精神障碍奠定重要基础。

DESCRIPTION (provided by applicant): Dysfunctions of the basal ganglia (BG), such as Parkinson's disease, obsessive-compulsive disorder, and substance abuse, produce a number of motor and cognitive deficits. Nevertheless, current therapeutic interventions are mostly empirical, and their underlying mechanisms remain poorly understood. This reflects our poor knowledge about how different subdivisions of the basal ganglia interact so that their outputs can adaptively modulate the activity of neurons in their downstream structures. So far, almost all influential models of the BG have proposed that they are involved in choosing appropriate actions (action selection) and altering the tendencies to choose different actions according to their previous outcomes (reinforcement learning). Nevertheless, how these functions are implemented across parallel anatomical pathways through the BG remains crudely understood, because only a small number of physiological studies have systematically compared the activity of neurons across different subdivisions of the BG during behavioral tasks designed to probe specific cognitive processes. Studies proposed in this application will investigate how signals distributed in three major components of the BG contribute to action selection and reinforcement learning. Specifically, we will focus on the output nuclei of the basal ganglia, namely, the internl segment of the globus pallidus (GPi) and the substantia nigra pars reticulata (SNr), in addition to the external segment of the globus pallidus (GPe) that is believed to exert substantial influences on all other components of the BG. The comparison of neural signals across different compartments of the BG is essential for understanding the nature of intra- and trans- basal-ganglia signal processing, including the role of the direct and indirect pathways. In our experiments, we will first test whether estimates for the outcomes expected from alternative actions are dynamically and continually updated in the GPe and GPi/SNr during a decision-making task. In particular, whether they show enhanced activity related to unexpected changes in the expected outcomes will be tested. Second, we will also test whether the signals related to rewards and penalties are encoded differentially across different subdivisions of the BG. The results from these studies will lay important foundations for developing more efficient treatments for a number of mental disorders resulting from BG dysfunctions.