Learning and Selection in the Basal Ganglia

基底神经节的学习和选择

• 批准号: 8753644
• 负责人: DAEYEOL LEE
• 金额: $ 24.31万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-11 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8753644
• 关键词: Adaptive Behaviors; Adverse effects; Anatomy; Animals; Area; Attention deficit hyperactivity disorder; Back; Basal Ganglia; Behavioral; Cell Nucleus; Cell physiology; Cognition; Cognitive; Cognitive deficits; Corpus striatum structure; Costs and Benefits; Decision Making; Deep Brain Stimulation; Direct Costs; Dopamine; Facilities and Administrative Costs; Foundations; Functional disorder; Globus Pallidus; Impairment; Influentials; Knowledge; Learning; Mediating; Mental disorders; Mink; Modeling; Motor; Nature; Neuromodulator; Neurons; Obsessive-Compulsive Disorder; Outcome; Output; Parkinson Disease; Pathway interactions; Pharmacotherapy; Physiological; Physiology; Play; Positioning Attribute; Prefrontal Cortex; Process; Psychological reinforcement; Public Health; Punishment; Rewards; Role; Signal Transduction; Societies; Source; Staging; Structure; Substance abuse problem; Substantia nigra structure; Synapses; Testing; Therapeutic Intervention; Time; Update; cognitive function; design; experience; insight; learned behavior; motor deficit; nervous system disorder; neurophysiology; public health relevance; relating to nervous system; research study; response; signal processing

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.

描述（由申请人提供）：基底神经节（BG）的功能障碍，例如帕金森氏病，强迫症和滥用药物，会产生许多运动和认知缺陷。然而，当前的治疗干预措施大多是经验性的，并且其潜在的机制仍然很少理解。这反映了我们对基底神经节相互作用的不同细分如何相互作用的不良知识，以便它们的输出可以适应下游结构中神经元的活性。到目前为止，BG的几乎所有有影响力的模型都提出，他们参与选择适当的行动（行动选择），并改变根据以前的结果（强化学习）选择不同行动的趋势。然而，如何在BG的平行解剖途径之间实现这些功能仍然是冷漠的，因为在旨在探测特定认知过程的行为任务中，只有少数生理研究系统地比较了BG不同细分的神经元的活性。本应用程序中提出的研究将研究信号如何分布在BG的三个主要组成部分中，从而有助于行动选择和增强学习。具体而言，我们还将重点关注基底神经节的输出核，即Globus Pallidus（GPI）的实习生段和底底nigra nigra pars enticulata（SNR） 据信，pallidus（GPE）的外部段对BG的所有其他成分产生了重大影响。 BG不同隔室的神经信号的比较对于理解内部和基底 - 基底 - 基底信号处理的性质至关重要，包括直接和间接途径的作用。在我们的实验中，我们将首先测试在决策任务期间，在GPE和GPI/SNR中对替代动作预期的结果的估计是否进行。特别是，将测试它们是否显示与预期结果意外变化有关的增强活动。其次，我们还将测试与奖励和罚款有关的信号是否在BG的不同细分之间进行了差异化。这些研究的结果将为开发更有效的治疗方法为BG功能障碍引起的许多精神疾病提供重要的基础。