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Dissecting the Action Learning Process with Dopaminergic Reinforcement

Award Number: R00NS112575
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2019
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Dissecting the Action Learning Process with Dopaminergic Reinforcement - Understanding the process by which animals learn to perform specific actions from rewarding experiences is important for identifying the neural and behavioral patterns that indicate system dysregulation; such knowledge can help lead to the development of diagnostics and therapy for conditions where action learning is impaired. Dopaminergic neurons and their targets have been implicated as major contributors to action learning. Though it is well known that stimulation of dopaminergic neurons can reinforce behavior, it is less clear how stimulated dopaminergic activities guide the animal to behaviorally search the world for the action that produces reward. The goal of this proposal is to characterize the role of dopaminergic activity in shaping behavior that hones in on a specific action or action sequences for reward. A key to this proposal is the combination of optogenetics and objective, unsupervised behavioral clustering to develop a closed loop reinforcement system in which reward in the form of dopaminergic stimulation is delivered to the VTA of animals as they learn to perform specific actions or action sequences. The K99 phase of the application will involve characterization of the behavioral patterns underlying single action and action sequence learning, followed by imaging of the dorsolateral striatum (known to represent the action space) in freely moving mice to understand the neural correlates of the action learning process. Functional circuit dissection will also be performed to elucidate which specific VTA projection pathways mediate action learning. Following mastering of these techniques, the applicant will enter the R00 phase and continue studying the role of specific VTA projection pathways on the action learning process. Chemogenetics in combination with closed loop reinforcement will be performed to dissect the pathways necessary for action learning. Neuronal activity imaging will then be performed on dopaminergic targets found to be important for action learning. The training plan, under the joint mentorship of Dr. Rui Costa and Dr. Stefano Fusi at Columbia University, will provide a complete set of neuroscience tools and the necessary career development resources for the applicant to obtain a faculty position and start an independent research program to explore the role of VTA dopaminergic neurons on the action learning process.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $224,094 )
2025	2025	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	2/20/2025	NON-COMPETING CONTINUATION	$224,094
														Subtotal = $224,094

Issue Date FY: 2024 ( Subtotal = $241,524 )
2024	2024	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/29/2024	EXTENSION WITH OR WITHOUT FUNDS	$224,097
2024	2024	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	4/12/2024	EXTENSION WITH OR WITHOUT FUNDS	$17,427
														Subtotal = $241,524

Grand Total All Awards = $465,618

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Dissecting the Action Learning Process with Dopaminergic Reinforcement

Award Number: R00NS112575

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2019

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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