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Impact of Prenatal Alcohol Exposure on CRF1R Mediated Neural Mechanisms and Social Behavior

Award Number: F32AA031185
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/01/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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Impact of Prenatal Alcohol Exposure on CRF1R Mediated Neural Mechanisms and Social Behavior - PROJECT SUMMARY/ABSTRACT Fetal Alcohol Spectrum Disorder is a set of diverse conditions caused by prenatal alcohol exposure (PAE) that can produce a wide variety of physical, behavioral, and intellectual deficits persisting throughout the lifespan. Importantly, PAE is also associated with deficits in emotional regulation, including increased non-social and social anxiety. However, the PAE-induced neurobiological changes that underlie this heightened vulnerability to develop increased social anxiety are not well understood. This gap in knowledge is problematic because a precise understanding of neuroadaptations resulting from PAE is necessary to develop targeted treatments for individuals experiencing PAE-related social impairments. Activity of corticotropin-releasing factor (CRF) and its receptor (CRF1R) in the medial subnucleus of the central amygdala (CeM), has long been known to regulate anxiety-like behavior, and disruption of the function of the CeM CRF system could contribute to increased social anxiety-like behavior in individuals exposed to PAE. Our lab has recently demonstrated that moderate PAE on gestational day (G)12, around the time of neurogenesis in the rat amygdala, increased social anxiety- like behavior in adult male rats. Additionally, G12 PAE disrupted CRF1R modulated inhibitory neurotransmission and non-social anxiety-like behavior in male rats, suggesting that moderate G12 PAE impairs CeM CRF1R regulated synaptic and behavioral function in adult male rats. These deficits could subsequently alter the function of CeM downstream projection targets, such as the periaqueductal gray, which is a brain region known to regulate defensive behaviors in response to threats, including social threats. This led us to the development of our central hypothesis, that moderate G12 PAE increases social anxiety-like behavior due to decreased function of the CRF1R positive (+) CeM-PAG projection in male rats. To test this, we will use whole-cell patch clamp electrophysiology to assess differences in neuronal excitability and neurotransmission in PAG-projecting CRF1R+ cells. Additionally, we will chemogenetically stimulate the CRF1R+ CeM-PAG projection prior to testing in a modified social interaction test to generate a measure of social anxiety-like behavior. Finally, we will further explore the possibility that the PAG underlies PAE-induced social impairments by assessing differences in cellular activation in the PAG following social interaction testing in male and female rats. The proposed experiments will expand our understanding of PAE-induced alterations in neural mechanisms, how these alterations relate to social anxiety-like behavior, and provide evidence to inform future studies designed to investigate the neuroadaptations resulting from moderate PAE. Additionally, successful completion of the goals outlined in this proposal will provide me with training in cutting-edge techniques, science communication, and mentoring that will prepare me for a career as an independent scientist.


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 = $0 )
2026	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	4400 VESTAL PKWY E	BINGHAMTON	NY	13902	BROOME	USA	Alcohol Research Programs	000	2	2/24/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $74,284 )
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	4400 VESTAL PKWY E	BINGHAMTON	NY	13902	BROOME	USA	Alcohol Research Programs	000	2	5/1/2024	NON-COMPETING CONTINUATION	$74,284
														Subtotal = $74,284

Issue Date FY: 2023 ( Subtotal = $69,080 )
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	4400 VESTAL PKWY E	BINGHAMTON	NY	13902	BROOME	USA	Alcohol Research Programs	000	1	4/13/2023	NEW	$69,080
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	4400 VESTAL PKWY E	BINGHAMTON	NY	13902	BROOME	USA	Alcohol Research Programs	001	1	4/13/2023	NEW	$0
														Subtotal = $69,080

Grand Total All Awards = $143,364

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Impact of Prenatal Alcohol Exposure on CRF1R Mediated Neural Mechanisms and Social Behavior

Award Number: F32AA031185

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/01/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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