# NEURAL CIRCUITRY MEDIATING BEHAVIORAL FLEXIBILITY

> **NIH NIH R00** · ROWAN UNIVERSITY SCHOOL/OSTEOPATHIC MED · 2020 · $248,990

## Abstract

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.

## Key facts

- **NIH application ID:** 10055804
- **Project number:** 4R00DA042934-03
- **Recipient organization:** ROWAN UNIVERSITY SCHOOL/OSTEOPATHIC MED
- **Principal Investigator:** Elizabeth A West
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,990
- **Award type:** 4N
- **Project period:** 2020-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10055804

## Citation

> US National Institutes of Health, RePORTER application 10055804, NEURAL CIRCUITRY MEDIATING BEHAVIORAL FLEXIBILITY (4R00DA042934-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10055804. Licensed CC0.

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