A Function for the Entopeduncular Nucleus in Motivated Behavior

内脚核在动机行为中的功能

• 批准号: 10553248
• 负责人: Michael L Wallace
• 金额: $ 24.9万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-18 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10553248
• 关键词: Animals; Basal Ganglia; Behavior; Behavioral; Brain; Brain region; Categories; Cell Nucleus; Data; Defect; Disease; Drug Addiction; Environment; Fiber; Fiber Optics; Functional disorder; Future; Ganglia; Globus Pallidus; Glutamates; Goals; Habenula; Human; Huntington Disease; Image; Imaging Techniques; Individual; Lateral; Learning; Left; Location; Mammals; Mental Depression; Mentors; Methods; Monitor; Motor; Movement; Mus; Negative Reinforcements; Neurons; Neurotransmitters; Nose; Obsessive-Compulsive Disorder; Optics; Outcome; Output; Parkinson Disease; Parvalbumins; Performance; Phase; Photometry; Play; Population; Positioning Attribute; Primates; Property; Psychological reinforcement; Research Personnel; Rewards; Role; Sensory; Somatostatin; Synapses; Synaptic plasticity; Techniques; Testing; Thalamic structure; Training; Vertebrates; Water; behavior change; calcium indicator; career; cell type; computer program; design; endopeduncular nucleus; experience; experimental study; fabrication; falls; flexibility; gamma-Aminobutyric Acid; high reward; human disease; implantation; in vivo; insight; motivated behavior; neurotransmission; neurotransmitter release; optical fiber; optogenetics; sensory integration; sensory stimulus; skills

Animals select actions based on incoming sensory information and past experience to achieve goals. As a result of these experiences, they modify their behavioral selection to promote the repetition of actions associated with positive outcomes and suppress those associated with bad outcomes. In mammals, the basal ganglia (BG) are crucial reinforcement learning and action selection and are defective in a wide range of human disorders such as Parkinson's disease and drug addiction. The entopeduncular nucleus (globus pallidus internus in primates) is an output nucleus of the BG, but its role in many of these functions ascribed to the BG has remained enigmatic. Recent findings have implicated the EP in negative reinforcement and aversion. However, the activity neuronal subtypes within the EP in a freely moving animal performing a motivated behavior are unknown. For this proposal I will investigate role of distinct EP neuronal classes in a behavioral task that requires flexible relationships between sensory stimuli and motor action. First, I will monitor activity of EP neurons during performance of the behavioral task, I will then test the causal relationship between activity of EP neuron subclasses and behavioral performance. Finally, I will explore the requirement for neurotransmitter release and synaptic plasticity in EP circuits for normal EP function. These experiments will define the role for EP neuronal subclasses in behavioral task that requires flexible relationships between sensory stimuli and motor action. Moreover, these studies will clarify the role EP circuitry may play in Parkinson's disease where action selection and execution are perturbed. During this project I will receive training in optics, in vivo optogenetics, computer programming, and quantitative behavioral techniques from experts in the field. These techniques and skills will allow me to successfully complete all of the proposed experimental aims and prepare myself for a career as an independent researcher.

动物根据传入的感官信息和过去的经验选择行动来实现目标。作为这些经历的结果，他们修改了自己的行为选择，以促进与积极结果相关的行为的重复，并抑制与坏结果相关的行为。在哺乳动物中，基底神经节（BG）是至关重要的强化学习和行动选择，并且在许多人类疾病（如帕金森病和药物成瘾）中存在缺陷。髓内核（灵长类动物的内苍白球）是BG的输出核，但它在BG的许多功能中的作用仍然是谜。最近的研究结果表明，EP与负强化和厌恶有关。然而，在自由运动的动物进行动机行为时，其活动神经元亚型尚不清楚。对于这个建议，我将研究不同的EP神经元类别在需要感觉刺激和运动动作之间灵活关系的行为任务中的作用。首先，我将在行为任务执行过程中监测EP神经元的活动，然后我将测试EP神经元子类活动与行为表现之间的因果关系。最后，我将探讨脑电图回路中神经递质释放和突触可塑性对正常脑电图功能的要求。这些实验将明确EP神经元亚类在行为任务中的作用，这些任务需要感觉刺激和运动动作之间的灵活关系。此外，这些研究将阐明脑电回路在帕金森病中可能发挥的作用，在帕金森病中，行动选择和执行受到干扰。在这个项目中，我将接受该领域专家在光学、体内光遗传学、计算机编程和定量行为技术方面的培训。这些技术和技能将使我成功地完成所有提出的实验目标，并为自己作为一名独立研究人员的职业生涯做好准备。