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Zona Incerta Contributions to Reward and Cocaine Addiction

Award Number: R01DA047269
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Zona Incerta Contributions to Reward and Cocaine Addiction - The zona incerta (ZI), or “zone of uncertainty”, is a poorly-characterized structure in the subthalamus. The caudal ZI and the adjacent subthalamic nucleus (STN) have been implicated in impulsive and motivational disorders in a subset of patients with Parkinson's disease (PD), and recent work has shown that optogenetic activation of the ZI robustly induces binge-like eating behavior in mice. Thus, both human and animal studies point to an unappreciated role for the ZI in regulating motivational and behavioral disorders. However, the underlying mechanisms remain largely unexplored. Recently, rabies-based, whole-brain monosynaptic retrograde mapping has revealed that the ZI sends projections to the ventral tegmental area (VTA). VTA dopamine and GABA neurons play a critical role in reward, motivation and addiction. We propose to test the hypothesis that the ZI regulates motivated and addictive behavior via its direct projection to the VTA. In this proposal, we will apply a variety of cutting-edge tools including viral-genetic anatomic and optogenetic circuit- mapping, optogenetic and chemogenetic stimulation and inhibition, electrophysiology, and other techniques to comprehensively study the underlying connectivity and physiology of the ZI-VTA pathway. Overall, our objectives include the following: characterize the cell type-specific connectivity between the ZI and the VTA using modern anatomic tools and electrophysiology (Aim I); determine how these connections affect neuronal activity in the major cell types of the VTA, and dopamine release in the nucleus accumbens, in vivo (Aim II); and determine how optogenetic and chemogenetic modulation of these pathways can drive or disrupt natural reward and cocaine reward-related behaviors (Aim III). These comprehensive studies will provide mechanistic insight into a structure and pathway of which very little is known. Completion of the proposed studies will not only identify novel neural substrates of reward and motivation, but will fill a knowledge gap that may ultimately lead to improved treatments for motivational and addictive disorders.


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 = -$4,196 )
2026	2023	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Drug Use and Addiction Research Programs	000	5	12/9/2025	NON-COMPETING CONTINUATION	-$4,196
														Subtotal = -$4,196

Issue Date FY: 2023 ( Subtotal = $365,750 )
2023	2023	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Drug Use and Addiction Research Programs	000	5	7/21/2023	NON-COMPETING CONTINUATION	$365,750
														Subtotal = $365,750

Issue Date FY: 2022 ( Subtotal = $365,750 )
2022	2022	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Drug Use and Addiction Research Programs	000	4	6/22/2022	NON-COMPETING CONTINUATION	$365,750
														Subtotal = $365,750

Issue Date FY: 2021 ( Subtotal = $365,750 )
2021	2021	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Drug Use and Addiction Research Programs	000	3	6/26/2021	NON-COMPETING CONTINUATION	$365,750
														Subtotal = $365,750

Issue Date FY: 2020 ( Subtotal = $346,500 )
2020	2020	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Drug Use and Addiction Research Programs	000	2	6/12/2020	NON-COMPETING CONTINUATION	$346,500
														Subtotal = $346,500

Issue Date FY: 2019 ( Subtotal = $346,500 )
2019	2019	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Drug Use and Addiction Research Programs	000	1	9/5/2019	NEW	$346,500
														Subtotal = $346,500

Grand Total All Awards = $1,786,054

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Zona Incerta Contributions to Reward and Cocaine Addiction

Award Number: R01DA047269

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/15/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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