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Neural circuit regulation of ramping activity in dopamine neurons

Award Number: R01DA055075
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Neural circuit regulation of ramping activity in dopamine neurons - Project Summary Ventral striatal dopamine progressively rises as rodents navigate toward spatially distant rewards, a surprising recent finding that was not anticipated by temporal difference learning models of dopamine function. Ramping dopamine release in the ventral striatum reflects the value and proximity of goals, scaling by the value of the reward and stretching or compressing in different environments to span the distance between start and goal locations. Activity in ventral tegmental area (VTA) dopamine neurons also ramps up as animals approach goals, but the strength and persistence of ramping activity in dopamine neurons depends on both the use of an internal model of goal proximity and on the amount of task experience. Ramping activity in dopamine neurons appears immediately when naïve mice run toward newly-discovered rewards in spatial environments, and ramps gradually fade away over several days of training if sensory information about reward proximity is available. When an internal representation of progress toward the goal is required, however, robust ramping activity in dopamine neurons persists indefinitely. These findings suggest the hypothesis that ramping activity in VTA dopamine neurons depends on the use of brain regions that represent an internal model of the environment and current progress toward goals. We propose to test this overarching hypothesis by addressing the following specific aims: 1) Test the hypothesis that neural activity in the ventral hippocampus contributes to ramping activity in midbrain dopamine neurons. 2) Compare the evolution of ramping activity in VTA dopamine neurons with the evolution of ramping dopamine release in the ventral striatum. 3) Characterize neural activity in VTA GABA neurons during spatial and non-spatial navigation to rewards. Understanding the neural mechanisms that underlie ramping activity in dopamine neurons will have relevance for the neural basis of cognitive control, goal-directed behavior, perseverance, and spatial learning. Our findings will provide valuable information relevant for mental disorders associated with dysfunction in these abilities including attention deficit hyperactivity disorder, obsessive compulsive disorder, depression, and addiction.


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: 2026 ( Subtotal = $349,500 )
2026	2026	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Drug Use and Addiction Research Programs	000	5	5/12/2026	NON-COMPETING CONTINUATION	$349,500
														Subtotal = $349,500

Issue Date FY: 2025 ( Subtotal = $2,216 )
2025	2025	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Drug Use and Addiction Research Programs	002	4	4/10/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$34,835
2025	2025	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Drug Use and Addiction Research Programs	001	4	3/18/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$313,540
2025	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Drug Use and Addiction Research Programs	003	3	4/11/2025	NON-COMPETING CONTINUATION	$0
2025	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Drug Use and Addiction Research Programs	000	3	3/17/2025	NON-COMPETING CONTINUATION	-$346,159
														Subtotal = $2,216

Issue Date FY: 2024 ( Subtotal = $346,160 )
2024	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Drug Use and Addiction Research Programs	001	3	4/25/2024	NON-COMPETING CONTINUATION	$34,616
2024	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Drug Use and Addiction Research Programs	000	3	2/8/2024	NON-COMPETING CONTINUATION	$311,544
														Subtotal = $346,160

Issue Date FY: 2023 ( Subtotal = $346,160 )
2023	2023	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Drug Use and Addiction Research Programs	000	2	2/27/2023	NON-COMPETING CONTINUATION	$346,160
														Subtotal = $346,160

Issue Date FY: 2022 ( Subtotal = $346,160 )
2022	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Drug Use and Addiction Research Programs	000	1	4/21/2022	NEW	$346,160
														Subtotal = $346,160

Grand Total All Awards = $1,390,196

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Neural circuit regulation of ramping activity in dopamine neurons

Award Number: R01DA055075

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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