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Isolation of brain reward circuits using peptidergic systems

Award Number: R01DA044315
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2018
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Isolation of brain reward circuits using peptidergic systems - Project Summary The neurotransmitter dopamine provides an important modulatory signal that facilitates a myriad of brain functions. The heterogeneity of neurons in the VTA has long been appreciated, but therapeutic strategies targeting the system are still based on a monolithic perspective. Recent advances in genetics-based methods have provided new approaches to resolving the molecular pathways that regulate the intrinsic properties of these cells that underlie their distinct functions and likely confer unique pharmacological sensitivities. Using single nuclear RNA sequencing, we defined unique genetic signatures within specific cell types that we hypothesize contributes to their functionality. Specifically, we identified ion channel subunits that are differentially expressed in dopamine subpopulations that confer unique electrophysiological properties to essential voltage-gated potassium channels that we hypothesize contributes to differences in the intrinsic excitability of these cells. We have also defined the unique circuit connectivity of these cells. We will utilize a combination of genetic and pharmacological approaches to understand how the regulation of ion channels and circuit connections contributes to the specialization of these cell types. In addition to the genetic profile of specific populations, we have identified a neuropeptide receptor that is expressed in subsets of the major projection subpopulations. Activation of neurons that express this receptor is minimally sufficient to promote reinforcement, but the function of this receptor and its intracellular signaling in this context remain largely unknown. To address this, we will use a combination of pharmacology and molecular genetics approaches to understand the intracellular signaling associated with this receptor that confers its function within dopamine neurons. Collectively, the aims of this proposal will provide important new insight into the molecular pharmacology of dopamine subpopulations.


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 = $417,168 )
2026	2026	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	000	9	4/2/2026	NON-COMPETING CONTINUATION	$417,168
														Subtotal = $417,168

Issue Date FY: 2025 ( Subtotal = $417,168 )
2025	2025	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	001	8	4/14/2025	NON-COMPETING CONTINUATION	$41,716
2025	2025	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	000	8	3/24/2025	NON-COMPETING CONTINUATION	$375,452
														Subtotal = $417,168

Issue Date FY: 2024 ( Subtotal = $417,168 )
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	000	7	3/20/2024	NON-COMPETING CONTINUATION	$375,452
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	001	7	4/24/2024	NON-COMPETING CONTINUATION	$41,716
2024	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	003	6	4/29/2024	COMPETING CONTINUATION	$9,924
2024	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	002	5	4/29/2024	NON-COMPETING CONTINUATION	-$9,924
														Subtotal = $417,168

Issue Date FY: 2023 ( Subtotal = $417,168 )
2023	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	001	6	5/30/2023	COMPETING CONTINUATION	$417,168
2023	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	000	5	5/29/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $417,168

Issue Date FY: 2022 ( Subtotal = $221,660 )
2022	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	001	5	2/22/2022	NON-COMPETING CONTINUATION	$305,254
2022	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	002	5	3/18/2022	NON-COMPETING CONTINUATION	$33,918
2022	2021	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	000	4	10/19/2021	SUPPLEMENT FOR EXPANSION	-$117,512
														Subtotal = $221,660

Issue Date FY: 2021 ( Subtotal = $457,349 )
2021	2021	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	000	4	2/11/2021	NON-COMPETING CONTINUATION	$339,679
2021	2021	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	001	4	2/12/2021	SUPPLEMENT FOR EXPANSION	$117,670
														Subtotal = $457,349

Issue Date FY: 2020 ( Subtotal = $457,833 )
2020	2020	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	001	3	7/17/2020	SUPPLEMENT FOR EXPANSION	$117,670
2020	2020	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	000	3	2/26/2020	NON-COMPETING CONTINUATION	$340,163
														Subtotal = $457,833

Issue Date FY: 2019 ( Subtotal = $346,337 )
2019	2019	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	000	2	2/28/2019	NON-COMPETING CONTINUATION	$346,337
														Subtotal = $346,337

Issue Date FY: 2018 ( Subtotal = $347,570 )
2018	2018	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	000	1	4/6/2018	NEW	$347,570
														Subtotal = $347,570

Grand Total All Awards = $3,499,421

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Isolation of brain reward circuits using peptidergic systems

Award Number: R01DA044315

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/15/2018

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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