A Function for the Entopeduncular Nucleus in Motivated Behavior

内脚核在动机行为中的功能

基本信息

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
项目类别：
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

项目摘要

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以实现目标。由于这些经历，他们改变了自己的行为选择，以促进与积极结果相关的行为的重复，并抑制与不良结果相关的行为。在哺乳动物中，基底神经节（BG）对于强化学习和动作选择至关重要，并且在帕金森病和毒瘾等多种人类疾病中存在缺陷。内脚核（灵长类动物苍白球内部核）是 BG 的输出核，但其在 BG 的许多功能中的作用仍然是个谜。最近的研究结果表明 EP 与负强化和厌恶有关。然而，在自由活动的动物执行动机行为时，EP 内的活动神经元亚型尚不清楚。对于这个提案，我将研究不同 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，我将在执行行为任务期间监测 EP 神经元的活动，然后测试 EP 神经元子类的活动与行为表现之间的因果关系。最后，我将探讨正常 EP 功能对 EP 回路中神经递质释放和突触可塑性的要求。这些实验将定义 EP 神经元亚类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。此外，这些研究将阐明 EP 电路在帕金森病（行动选择和执行受到干扰）中可能发挥的作用。在这个项目期间，我将接受该领域专家的光学、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能够成功完成所有提出的实验目标，并为自己作为一名独立研究员的职业生涯做好准备。