A function for the Entopeduncular Nucleus In Motivated Behavior

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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.