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Effects of adolescent social isolation on adult decision making and corticostriatal circuitry

Award Number: K01MH127306
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 03/15/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Effects of adolescent social isolation on adult decision making and corticostriatal circuitry - PROJECT SUMMARY/ABSTRACT Adolescence is a particularly important period in social and cognitive development, characterized in part by rapid increases in exploration, social interaction, and neural connectivity. Social isolation in adolescence has a clear, profound impact on a wide range of behavioral and physiological endpoints extending into adulthood. The overarching research goal of this proposal is to elucidate how adolescent social isolation in male and female mice alters value-based decision making in adulthood, as well as the underlying corticostriatal circuitry driving these complex goal-directed behaviors. This work is timely and vitally important as COVID-19 has subjected an increasing number of adolescents to social isolation through school closures and stay-at-home orders. A first aim of this proposal is to use operant tasks to systematically investigate how adolescent social isolation impacts how mice later value reward benefits and integrate expected costs during decision making. Preliminary data suggests that adolescent social isolation amplifies reward value, but specific aspects of decision-making behavior will be disentangled with computational modeling of value-based choice. The second aim builds on this behavioral work to test the hypothesis that adolescent social isolation disrupts corticostriatal circuitry and striatal output during adult value-based decision-making. A distributed neural network is engaged during decision- making, and the dorsomedial striatum (DMS) is a key node in this network. Prefrontal inputs to the DMS from the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) are critically involved in action selection and outcome valuation, respectively. All three of these nodes undergo maturation and refinement during adolescence, and adolescent social isolation disrupts this development. However, how this impacts adult corticostriatal function remains unknown. Using in vivo electrophysiology, local field potential (LFP) and single- unit recordings will be used to test how adolescent social isolation affects synaptic strength and connectivity from these cortical regions to the DMS during value-based decision-making behavior. This work proposed in the Mentored Research Scientist Development Award will provide Dr. Elizabeth Holly with training in computational modeling of decision-making behavior and in vivo electrophysiology, which will be an important part of the foundation of her independent research career. By completion of this Award, the goal is for Dr. Holly to transition to a tenure-track faculty position and apply for an R01. The mentorship team Dr. Holly has assembled will ensure her successful training in these techniques, and prepare her to transition to her own independent research laboratory.


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 = $233,874 )
2024	2024	RUTGERS, THE STATE UNIVERSITY	123 WASHINGTON ST	NEWARK	NJ	07102	ESSEX	USA	Mental Health Research Grants	003	5	6/14/2024	NON-COMPETING CONTINUATION	$179,874
2024	2024	RUTGERS, THE STATE UNIVERSITY	123 WASHINGTON ST	NEWARK	NJ	07102	ESSEX	USA	Mental Health Research Grants	000	4	4/29/2024	SUPPLEMENT FOR EXPANSION	$54,000
2024	2022	RUTGERS, THE STATE UNIVERSITY	123 WASHINGTON ST	NEWARK	NJ	07102	ESSEX	USA	Mental Health Research Grants	002	3	6/13/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$38,229
2024	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	001	2	6/13/2024	NON-COMPETING CONTINUATION	-$38,229
														Subtotal = $233,874

Issue Date FY: 2023 ( Subtotal = $179,874 )
2023	2023	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	123 WASHINGTON ST STE 510	NEWARK	NJ	07102	ESSEX	USA	Mental Health Research Grants	002	4	6/23/2023	NON-COMPETING CONTINUATION	$179,874
2023	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	123 WASHINGTON ST STE 510	NEWARK	NJ	07102	ESSEX	USA	Mental Health Research Grants	001	3	5/11/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$113,971
2023	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	2	5/10/2023	NON-COMPETING CONTINUATION	-$113,971
														Subtotal = $179,874

Issue Date FY: 2022 ( Subtotal = $179,874 )
2022	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	2	6/13/2022	NON-COMPETING CONTINUATION	$179,874
														Subtotal = $179,874

Issue Date FY: 2021 ( Subtotal = $179,874 )
2021	2021	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	1	7/15/2021	NEW	$179,874
														Subtotal = $179,874

Grand Total All Awards = $773,496

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Effects of adolescent social isolation on adult decision making and corticostriatal circuitry

Award Number: K01MH127306

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 03/15/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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