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Sexually Dimorphic Vasopressin Circuits in the Control of Social Interest

Award Number: R01MH135553
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/03/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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Sexually Dimorphic Vasopressin Circuits in the Control of Social Interest - Project Summary Disorders of social behavior are increasingly prevalent and pose a substantial burden to society. These disorders often show sex differences in prevalence, expression, and severity. One explanation for these differences reflects dysfunction in the sexually differentiated social brain. A particularly relevant neuropeptide system in this respect is the arginine vasopressin (AVP) innervation of the brain, which shows marked sex differences across many species, including humans, and has been implicated in aggressive as well as affiliative behavior. Indeed, the main receptor for AVP in the brain, V1aR, has been linked to social behavior, including that of humans. Despite the significance of this system, few studies have directly assessed how, when, and where AVP and V1aR systems interact to influence social interest in adults. Here we focus on the interaction between the sexually dimorphic AVP cells of the bed nucleus of the stria terminalis (BNST) and its major target, the lateral septum (LS), an area with the highest expression of V1aR in vertebrate brains. In the first aim, we will test the necessity of LS V1aR cells for social interest by optogenetic inhibition of these cells or by genetically knocking out V1aR in LS. In addition, we will combine optogenetic stimulation of BNST AVP cells and V1aR knockdown in LS in vivo and ex vivo to test whether AVP from the BNST specifically acts on LS V1aR cells to alter behavior and cellular physiology. The second aim will test whether V1aRs in the LS are sufficient for driving social interest by optogenetic excitation of these cells. The third aim will test whether V1aR cells in the LS encode social interest in a sexually dimorphic manner, and whether this encoding is altered by BNST AVP cell activity (via chemogenetic inhibition). This project will significantly enhance our mechanistic understanding of how the brain controls social behavior differently in males and females and may give insight as to why many behavioral disorders show striking sex differences in morbidity. Although recently major advances have been made in understanding the neural basis of social behavior, how such behavior is controlled differently in males and females is, by and large, unknown. This grant will address these issues.


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 = $731,379 )
2026	2026	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Mental Health Research Grants	000	3	7/1/2026	NON-COMPETING CONTINUATION	$731,379
														Subtotal = $731,379

Issue Date FY: 2025 ( Subtotal = $731,379 )
2025	2025	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Mental Health Research Grants	000	2	6/15/2025	NON-COMPETING CONTINUATION	$731,379
														Subtotal = $731,379

Issue Date FY: 2024 ( Subtotal = $727,479 )
2024	2024	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Mental Health Research Grants	000	1	9/3/2024	NEW	$727,479
														Subtotal = $727,479

Grand Total All Awards = $2,190,237

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Sexually Dimorphic Vasopressin Circuits in the Control of Social Interest

Award Number: R01MH135553

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/03/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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