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.

Public Health Relevance

The basal ganglia are a group of brain regions critically involved in integrating sensory and motor inputs to select appropriate actions. Their dysfunction in implicated in a broad range of human diseases from Parkinson's to depression and Obsessive Compulsive Disorder. In this proposal I will investigate the role the basal ganglia has controlling action selection in a changing sensory environment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Career Transition Award (K99)
Project #
1K99NS105883-01A1
Application #
9664282
Study Section
Neurological Sciences Training Initial Review Group (NST)
Program Officer
Chen, Daofen
Project Start
2018-09-18
Project End
2020-08-31
Budget Start
2018-09-18
Budget End
2019-08-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Harvard Medical School
Department
Biology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code