Monday, October 13, 2025 10/13/2025

Role of neurexin in social adaptation and amygdala plasticity

Award Number: R01MH137651
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/05/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2029

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Role of neurexin in social adaptation and amygdala plasticity - Project summary Social relationships benefit mental and physical health, while poor quality social interactions are associated with worse health and higher mortality. The abilities that underlie social function are impaired in Autism Spectrum Disorder (ASD). There has been substantial progress in identifying genes that are associated ASD. But the link between ASD genetic factors and core social disruptions is unclear. Even in non-ASD individuals it is not clear how these genes influence social behavior. To understand how these genes influence social behavior, we must uncover how they impact the neural circuits that underlie social function. Many key social functions are traced to a network of connected brain regions that is similar in rodents and primates. This presents an opportunity to determine the impact of high-risk ASD genes on the function of key connections within this social network. Prior research demonstrates that prefrontal cortical (PFC) connections to amygdala, particularly anterior cingulate (ACC) excitatory projections to basolateral amygdala (BLA), play a fundamental role in encoding social information and motivating social behaviors. Social behavior must be flexible in response to shifts of extrinsic conspecific behavior and intrinsic social drive. ACC-BLA guides behavioral adaptations during these shifts. This behavioral flexibility likely requires synaptic plasticity. NRXN1 (Nrxn1 in rodents) is a high confidence ASD gene, and Nrxn1 disruption replicably impairs social behaviors in rodents and weakens PFC-BLA synapses. There is much known about the importance of neurexin 1 protein in synaptic functions, but it is not understood why Nrxn1 disruption leads to social impairments. In this project we propose that neurexin 1 at PFC-BLA synapses is positioned to influence synaptic plasticity during social experience. A goal of this research is to determine if neurexin 1 impacts rodent social behaviors by preferential modulation of ACC-BLA synapses. We hypothesize that nrxn1 has circuit-specific actions on ACC-BLA and, through this, nrxn1 contributes to flexibility of social behavior and ACC-BLA plasticity. This will be tested using a combination of acute interference with neurexin 1, gene knockouts and circuit-specific knockdown in rats, while measuring social behaviors that rely on PFC-BLA integrity, BLA responses to social stimuli, and PFC-BLA synaptic function. These studies will provide us with a new understanding of the role of neurexin 1 in modulation of a PFC-BLA circuit that is required for social flexibility. This novel information would help bridge a known genetic social influencer with the neurobiology of social function.


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 = $528,357 )
2025	2025	ROSALIND FRANKLIN UNIVERSITY OF MEDICINE & SCIENCE	3333 GREEN BAY RD	NORTH CHICAGO	IL	60064	LAKE	USA	Mental Health Research Grants	001	2	9/19/2025	NON-COMPETING CONTINUATION	$79,253
2025	2025	ROSALIND FRANKLIN UNIVERSITY OF MEDICINE & SCIENCE	3333 GREEN BAY RD	NORTH CHICAGO	IL	60064	LAKE	USA	Mental Health Research Grants	000	2	3/11/2025	NON-COMPETING CONTINUATION	$449,104
														Subtotal = $528,357

Issue Date FY: 2024 ( Subtotal = $528,357 )
2024	2024	ROSALIND FRANKLIN UNIVERSITY OF MEDICINE & SCIENCE	3333 GREEN BAY RD	NORTH CHICAGO	IL	60064	LAKE	USA	Mental Health Research Grants	000	1	8/2/2024	NEW	$528,357
														Subtotal = $528,357

Grand Total All Awards = $1,056,714

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Role of neurexin in social adaptation and amygdala plasticity

Award Number: R01MH137651

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/05/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2029

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