Learning and Selection in the Basal Ganglia

描述(申请人提供)：基底节(BG)功能障碍，如帕金森氏症、强迫症和药物滥用，会产生一些运动和认知障碍。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节不同部分如何相互作用的了解不足，以便它们的输出可以自适应地调节其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，他们参与选择适当的动作(动作选择)，并根据先前的结果改变选择不同动作的倾向(强化学习)。然而，这些功能是如何通过BG在平行的解剖路径上实现的仍然是粗略的理解，因为只有少量的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中，BG不同部分的神经元的活动。这项申请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动作选择和强化学习。具体地说，我们将关注基底节的输出核，即苍白球内侧段(GPI)和黑质网状部(SNR)。 苍白球(GPE)的外部部分，被认为对BG的所有其他组成部分产生重大影响。BG不同区域的神经信号的比较对于理解基底节内和跨基底节信号处理的本质，包括直接和间接通路的作用是至关重要的。在我们的实验中，我们将首先测试在决策任务期间，对替代行动预期结果的估计是否在GPE和GPI/SNR中动态且持续更新。特别是，它们是否显示出与预期结果的意外变化有关的活动增强将受到测试。其次，我们还将测试与奖惩相关的信号是否在BG的不同细分中进行了差异编码。这些研究的结果将为开发更有效的治疗由BG功能障碍引起的一些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.