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经验的，其潜在机制仍然知之甚少。这反映了我们对基底神经节的不同分支如何相互作用，从而使它们的输出能够自适应地调节其下游结构中的神经元活动的了解不足。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平行的解剖通路通过BG实现的，仍然知之甚少，因为只有少数生理学研究系统地比较了在旨在探测特定认知过程的行为任务中BG不同细分的神经元的活动。本应用中提出的研究将调查分布在BG的三个主要组成部分的信号如何有助于行动选择和强化学习。具体来说，我们将重点关注基底节区的输出核，即苍白球内段（GPi）和网状黑质（SNr）

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.