A function for the Entopeduncular Nucleus In Motivated Behavior

动物根据传入的感官信息和过去的经验来选择动作来实现目标。作为这些经历的结果，他们改变了自己的行为选择，以促进与积极结果相关的行动的重复，并抑制与不良结果相关的行动。在哺乳动物中，基底节(BG)是重要的强化学习和动作选择，在帕金森氏病和药物成瘾等广泛的人类疾病中存在缺陷。内侧脚核(灵长类动物的苍白球内核)是BG的输出核，但它在BG的许多功能中所起的作用仍然是个谜。最近的研究结果表明，EP与负性强化和厌恶有关。然而，在自由活动的动物进行动机行为的EP中，神经元亚型的活动尚不清楚。对于这项提议，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所扮演的角色。首先，我将监测行为任务执行过程中EP神经元的活动，然后我将检验EP神经元亚类的活动与行为表现之间的因果关系。最后，我将探讨正常的EP功能对EP回路中神经递质释放和突触可塑性的要求。这些实验将确定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所扮演的角色。此外，这些研究将阐明EP回路在帕金森氏症中可能扮演的角色，帕金森病的动作选择和执行受到干扰。在这个项目中，我将从该领域的专家那里接受光学、活体光遗传学、计算机编程和定量行为技术方面的培训。这些技巧和技能将使我能够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。

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.