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Dissecting the role of vasopressin in regulating the critical period for social reward learning

Award Number: R01HD098184
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Dissecting the role of vasopressin in regulating the critical period for social reward learning - PROJECT SUMMARY: The overall objective of the studies proposed in this revised R01 application is to elucidate the molecular mechanisms underlying regulation of social brain development, a first step in a larger project aimed at identifying circuit based approaches which improve therapeutics for neurodevelopmental disorders characterized by social impairments, as well as diseases which may be the consequence of social injury during brain development. Based on extensive preliminary findings, our overall hypothesis is that developmental upregulation of arginine vasopressin (AVP) signaling constrains social reward learning to a critical period, and that these functions are enabled by presynaptic AVP receptors in the ventral pallidum (vPD). The goal of this R01 application is to explore this understudied area and to develop tools to test our hypothesis directly in vivo and ex vivo. Three specific aims have been proposed to achieve our goal. Specifically: Specific Aim 1: To map and characterize the AVP neuronal projection from the hypothalamus to the vPD. Here we will test the hypothesis that the vPD receives a parvocellular AVP neuronal projection from the hypothalamus. Specific Aim 2: To determine whether AVP evokes synaptic plasticity in the vPD across development. Here we will test the hypothesis that the magnitude of AVP induced synaptic plasticity in the vPD is increased across development. Specific Aim 3: To determine whether AVP1a receptors in the vPD are required for constraining the social reward learning critical period. Here we will test the hypothesis that AVP1a receptors in the vPD are required for the closure of the social reward learning critical period. We predict these studies will demonstrate the reciprocal regulation of OT and AVP as a mechanism underlying the establishment of a critical period for social reward learning. In addition, these studies are designed to identify a novel manipulation (blockade of the AVP1aR) that can reinstate social reward learning in adulthood, which will have important implications for future clinical trials of mechanism-based therapies for the treatment of autism, schizophrenia, addiction and post-traumatic stress disorder. Moreover, because these studies characterize a quantifiable measure of social reward learning (social conditioned place preference) that can be used in both humans and mice, they dramatically improve the translational validity of these studies for future development of therapeutic interventions.


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: 2024 ( Subtotal = $341,571 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Child Health and Human Development Extramural Research	000	5	11/28/2023	NON-COMPETING CONTINUATION	$310,519
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Child Health and Human Development Extramural Research	001	5	5/2/2024	NON-COMPETING CONTINUATION	$31,052
														Subtotal = $341,571

Issue Date FY: 2023 ( Subtotal = $345,021 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Child Health and Human Development Extramural Research	000	4	12/23/2022	NON-COMPETING CONTINUATION	$310,519
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Child Health and Human Development Extramural Research	001	4	2/27/2023	NON-COMPETING CONTINUATION	$34,502
														Subtotal = $345,021

Issue Date FY: 2022 ( Subtotal = $345,021 )
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Child Health and Human Development Extramural Research	000	3	11/22/2021	NON-COMPETING CONTINUATION	$310,518
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Child Health and Human Development Extramural Research	001	3	4/27/2022	NON-COMPETING CONTINUATION	$34,503
														Subtotal = $345,021

Issue Date FY: 2021 ( Subtotal = $345,021 )
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Child Health and Human Development Extramural Research	000	2	12/9/2020	NON-COMPETING CONTINUATION	$316,856
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Child Health and Human Development Extramural Research	001	2	2/4/2021	NON-COMPETING CONTINUATION	$28,165
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Child Health and Human Development Extramural Research	002	2	3/31/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $345,021

Issue Date FY: 2020 ( Subtotal = $352,063 )
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Child Health and Human Development Extramural Research	000	1	12/6/2019	NEW	$352,063
														Subtotal = $352,063

Grand Total All Awards = $1,728,697

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Dissecting the role of vasopressin in regulating the critical period for social reward learning

Award Number: R01HD098184

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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