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）功能障碍，例如帕金森病、强迫症和药物滥用，会产生许多运动和认知缺陷。然而，目前的治疗干预措施大多是经验性的，其潜在机制仍然知之甚少。这反映出我们对基底神经节的不同分支如何相互作用、如何使它们的输出能够自适应地调节下游结构中神经元的活动知之甚少。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，这些功能如何通过 BG 跨平行解剖通路实现仍然是粗略的了解，因为只有少数生理研究系统地比较了在旨在探测特定认知过程的行为任务期间 BG 不同分区的神经元活动。本申请中提出的研究将调查分布在 BG 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。具体来说，我们将重点关注基底神经节的输出核，即苍白球内段（GPi）和黑质网状部（SNr），此外 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。比较 BG 不同区室的神经信号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）至关重要。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 中动态且持续地更新。特别是，将测试它们是否表现出与预期结果的意外变化相关的增强活动。其次，我们还将测试与奖励和惩罚相关的信号是否在 BG 的不同细分中进行了差异编码。这些研究的结果将为开发更有效的治疗方法来治疗由 BG 功能障碍引起的许多精神障碍奠定重要基础。