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Registration of spatial gene expression in key nodes of reward-related circuitry in the human brain

Award Number: R01DA053581
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Registration of spatial gene expression in key nodes of reward-related circuitry in the human brain - PROJECT SUMMARY Drug addiction is highly comorbid with psychiatric disorders, particularly post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). These conditions share underlying genetic risk and are exacerbated by similar environmental factors, including exposure to stress and traumatic events. The dorsal anterior cingulate cortex (dACC), nucleus accumbens (NAc) and amygdala constitute key nodes of the brain’s reward circuitry, and perturbations in reward signaling are highly implicated in addiction, MDD and PTSD. The human dACC, NAc and amygdala have unique neuroanatomical features, which correspond to distinct biological functions. Given the close relationship between brain structure and function, precisely assigning gene expression to the spatial coordinates of individual cell populations within the cytoarchitecture can significantly advance our understanding of how dysregulation in these areas contributes to addiction and comorbid neuropsychiatric disorders. Towards this goal, we propose to generate detailed spatial transcriptomic maps, which will be combined with single-nucleus RNA sequencing (snRNA-seq) to register molecularly-defined cell types to their spatial coordinates, facilitating prediction of the anatomical locations of distinct neuronal classes of cells within the dACC, NAc and amygdala. These molecularly- and spatially-defined populations of cells will be associated with gene expression changes linked to substance use and comorbid neuropsychiatric disorders. We hypothesize that these regions have a precise molecular architecture that reveals 1) topographically organized and molecularly-defined cell types within layers of the dACC, and across sub-regions of the NAc and amygdala; 2) spatial-enrichment of genes associated with addiction and comorbid neuropsychiatric disorders. By generating the first transcriptome-scale spatial maps of the human dACC, NAc and amygdala, critical information about the molecular landscape of these regions within the architecture of the human brain will be generated. Our spatial registration approach will facilitate refined annotation of cell types in the human brain, and contribute to understanding addiction and comorbid neuropsychiatric disorders by identifying clinical associations with molecularly- and spatially-defined cell populations that can be targeted for prevention and treatment.


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 = $690,859 )
2025	2025	THE LIEBER INSTITUTE	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Drug Use and Addiction Research Programs	000	5	7/28/2025	NON-COMPETING CONTINUATION	$690,859
														Subtotal = $690,859

Issue Date FY: 2024 ( Subtotal = $681,004 )
2024	2024	THE LIEBER INSTITUTE	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Drug Use and Addiction Research Programs	000	4	7/24/2024	NON-COMPETING CONTINUATION	$681,004
														Subtotal = $681,004

Issue Date FY: 2023 ( Subtotal = $704,352 )
2023	2023	LIEBER INSTITUTE, INC.	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Drug Use and Addiction Research Programs	000	3	7/21/2023	NON-COMPETING CONTINUATION	$704,352
														Subtotal = $704,352

Issue Date FY: 2022 ( Subtotal = $796,604 )
2022	2022	LIEBER INSTITUTE, INC.	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Drug Use and Addiction Research Programs	001	2	7/19/2022	NON-COMPETING CONTINUATION	$796,604
2022	2021	LIEBER INSTITUTE, INC.	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Drug Use and Addiction Research Programs	000	1	7/19/2022	NEW	$0
														Subtotal = $796,604

Issue Date FY: 2021 ( Subtotal = $821,650 )
2021	2021	LIEBER INSTITUTE, INC.	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Drug Use and Addiction Research Programs	000	1	9/23/2021	NEW	$821,650
														Subtotal = $821,650

Grand Total All Awards = $3,694,469

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Registration of spatial gene expression in key nodes of reward-related circuitry in the human brain

Award Number: R01DA053581

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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