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Behavioral and neural mechanisms mediating social motivation in a rat model for ASD

Award Number: R01MH129310
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/16/2022
PERIOD OF PERFORMANCE END DATE: 10/31/2027

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Behavioral and neural mechanisms mediating social motivation in a rat model for ASD - Project Summary Autism spectrum disorder (ASD) is characterized by impaired social communication, often attributed to misreading of emotional cues. Despite progress toward understanding ASD, treatment options remain limited. This is partly due to limitations of animal models of ASD that fail to capture an essential aspect of the ASD condition – people with ASD have impairments in the motivation to engage in social interactions. We recently developed an operant model of choice between addictive drugs and social interaction, showing that operant social reward prevents drug self-administration and drug relapse. Our model highlights the importance of incorporating social factors into addiction neuroscience to mimic the human condition more closely. Our model allows us to directly assess both social reward and motivation to engage socially and the ethology of consequent naturalistic volitional social interactions using machine learning approaches for complex social behavior. The combination of a novel operant social model and advanced computational neuroethological analytical pipelines provides a unique toolkit to study the neurobiological mechanisms underlying social reward and potential disruption of social motivation in rodent model for ASD. The overarching aim of this proposal is to study the neural mechanisms mediating social motivation and the impact of Shank3 mutation (a rat model for ASD). In Aim 1, we will use open-source Python packages with graphical interface and intuitive workflow that uses pose-estimation, to create supervised and unsupervised machine learning-based predictive classifiers of social behavior. We hypothesize that Shank3-deficient rat model, but not wild-type rats will show aberrant social behaviors. In Aim 2, we will investigate the potential autism-like-induced shifts in social motivation using different behavioral approaches: social seeking, social progressive ratio, and social self-administration despite negative consequences. By combining our social self-administration model with a rat model of ASD, we will test the hypothesis that Shank3-deficient rats will show a disruption in social motivation behaviors, relative to wild-type rats. In Aim 3, we will use single-unit electrophysiological recording into the Medial Amygdala (MeA – a brain region critical for social behaviors) to identify units encoding rats’ social motivation or potential deficit in social motivation using a translational relevant social choice procedure. Additionally, we will use optogenetic approaches to reverse potential Shank3-dependent social motivation deficit in awake-behaving rats. These approaches will provide new frameworks on our understanding of the role of MeA for predicting aspects of future social-related events and for using these predictions to guide behavior within a rat model for ASD. Our proposal will provide new insights into behavioral and neural mechanisms mediating the motivation for social interaction in rat model for ASD.


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 = $436,018 )
2025	2025	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Mental Health Research Grants	000	3	11/1/2024	NON-COMPETING CONTINUATION	$436,018
														Subtotal = $436,018

Issue Date FY: 2024 ( Subtotal = $442,962 )
2024	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Mental Health Research Grants	001	2	6/27/2024	NON-COMPETING CONTINUATION	$44,296
2024	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Mental Health Research Grants	000	2	10/18/2023	NON-COMPETING CONTINUATION	$398,666
														Subtotal = $442,962

Issue Date FY: 2023 ( Subtotal = $432,962 )
2023	2023	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Mental Health Research Grants	000	1	12/15/2022	NEW	$432,962
														Subtotal = $432,962

Grand Total All Awards = $1,311,942

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Behavioral and neural mechanisms mediating social motivation in a rat model for ASD

Award Number: R01MH129310

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/16/2022

PERIOD OF PERFORMANCE END DATE: 10/31/2027

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