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NEURAL CIRCUITRY MEDIATING BEHAVIORAL FLEXIBILITY

Award Number: R00DA042934
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2020
PERIOD OF PERFORMANCE END DATE: 02/29/2024

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NEURAL CIRCUITRY MEDIATING BEHAVIORAL FLEXIBILITY - Project Summary/Abstract Balancing habitual and flexible strategies for navigating the environment is necessary for behavior that is both cognitively efficient and adaptive to change, and perturbations that disrupt this balance can result in significant behavioral impairments. For example, patients with substance abuse disorders often have difficulty altering their behavior to respond to changing outcomes, leading to poor decision-making. In the rat, a history of cocaine impairs the ability to adjust behavior away from reward-predictive cues following reward devaluation, a canonical measure of flexible behavior (i.e., cocaine leads to inflexible behavior). Interestingly, different striatal substrates underlie flexible, goal-directed behaviors (nucleus accumbens, NAc) and inflexible, habitual behaviors (dorsal lateral striatum, DLS), and proper balance between the NAc and DLS and their associated networks is critical for adaptive (flexible) but efficient (habitual) behavior. Thus, the current application will examine how a history of cocaine tips that balance and alters the neural network signaling that drives flexible and inflexible strategies. Balancing these subcortical networks requires cortical input. Specifically, distinct mPFC subregions (prelimbic cortex, PrL; and infralimbic cortex, IL) are differentially involved in flexible and inflexible strategies, respectively. Thus, to more fully characterize how a history of cocaine results in lasting behavioral impairments, I propose 4 specific aims to examine specific effects of a history of cocaine or effects of specific manipulations to networks driving flexibility. In aim 1, I will determine how a history of cocaine alters PrL and NAc cell firing and network dynamics (local field potentials) to reward predictive cues during learning and flexible behavior. In aim 2, I will determine if prelimbic cortical (PrL) inputs to the NAc core are causally linked to both flexible behavior and its neural encoding in the NAc. In aim 3, I will independently determine how a history of cocaine alters IL and DLS cell firing and network dynamics to reward predictive cues during learning and flexible behavior. Finally, in aim 4, I will determine if the IL to substania nigra (the primary input into DLS) pathway is causally linked to flexible behavior and neural encoding in the DLS. Together, these specific aims will characterize the balance between two parallel circuits (one involving PrL and NAc, and one involving IL and DLS) in behavioral flexibility and determine how a history of cocaine shifts this balance towards inflexible (habitual) circuitry and behavior. Understanding the neural circuitry underlying flexible vs habitual behavior and how neural encoding in these regions is altered by drug use will provide critical insight into new and more selective targets for therapeutic intervention for patients with substance abuse disorders.


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 = $0 )
2024	2022	ROWAN UNIVERSITY	201 MULLICA HILL RD	GLASSBORO	NJ	08028	GLOUCESTER	USA	Drug Use and Addiction Research Programs	000	5	8/12/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $569,820 )
2022	2022	ROWAN UNIVERSITY	201 MULLICA HILL RD RT 322	GLASSBORO	NJ	08028	GLOUCESTER	USA	Drug Use and Addiction Research Programs	000	5	2/18/2022	NON-COMPETING CONTINUATION	$248,355
2022	2022	ROWAN UNIVERSITY	201 MULLICA HILL RD RT 322	GLASSBORO	NJ	08028	GLOUCESTER	USA	Drug Use and Addiction Research Programs	001	5	4/6/2022	SUPPLEMENT FOR EXPANSION	$53,188
2022	2022	ROWAN UNIVERSITY	201 MULLICA HILL RD RT 322	GLASSBORO	NJ	08028	GLOUCESTER	USA	Drug Use and Addiction Research Programs	002	5	7/22/2022	SUPPLEMENT FOR EXPANSION	$268,277
														Subtotal = $569,820

Issue Date FY: 2021 ( Subtotal = $282,853 )
2021	2021	ROWAN UNIVERSITY	201 MULLICA HILL RD RT 322	GLASSBORO	NJ	08028	GLOUCESTER	USA	Drug Use and Addiction Research Programs	001	4	3/3/2021	NON-COMPETING CONTINUATION	$248,993
2021	2020	ROWAN UNIVERSITY	201 MULLICA HILL RD RT 322	GLASSBORO	NJ	08028	GLOUCESTER	USA	Drug Use and Addiction Research Programs	000	3	12/18/2020	EXTENSION WITH OR WITHOUT FUNDS	$33,860
														Subtotal = $282,853

Issue Date FY: 2020 ( Subtotal = $558,416 )
2020	2020	ROWAN UNIVERSITY	201 MULLICA HILL RD RT 322	GLASSBORO	NJ	08028	GLOUCESTER	USA	Drug Use and Addiction Research Programs	000	3	2/14/2020	EXTENSION WITH OR WITHOUT FUNDS	$248,990
2020	2020	ROWAN UNIVERSITY	201 MULLICA HILL RD RT 322	GLASSBORO	NJ	08028	GLOUCESTER	USA	Drug Use and Addiction Research Programs	001	3	6/19/2020	SUPPLEMENT FOR EXPANSION	$309,426
														Subtotal = $558,416

Grand Total All Awards = $1,411,089

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NEURAL CIRCUITRY MEDIATING BEHAVIORAL FLEXIBILITY

Award Number: R00DA042934

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2020

PERIOD OF PERFORMANCE END DATE: 02/29/2024

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