# NEURAL CIRCUITRY MEDIATING BEHAVIORAL FLEXIBILITY

> **NIH NIH R00** · ROWAN UNIVERSITY SCHOOL/OSTEOPATHIC MED · 2020 · $309,426

## Abstract

Project Summary
Balancing habitual and flexible strategies for navigating the environment is necessary for behavior
that is both cognitively efficient yet adaptive to change, and perturbations that disrupt this balance
can result in significant cognitive impairments. Significant work has focused on how patients with
substance abuse disorders (SUD) often shown difficulty altering their behavior to respond to
changing outcomes, leading to poor decision-making and disrupted cognitive function. These
deficits in cognitive function are linked to dampened prefrontal activity. The parent award is
aimed to determine how a history of cocaine alters the corticostriatal neural network signaling that
drives impaired cognitive flexibility. Critically, chronic history with drugs often leads to forms of
dementia, but little is known about how drugs of abuse and dementia are linked. This current
administrative supplement is aimed at examining how these circuits are altered in rat model of
Alzheimer’s disease (AD, TgF344-AD). Patients with AD show decreased grey matter in the
same brain regions linked to impaired cognitive flexibility in SUDs. We hypothesize that these
changes contribute to deficits in cognition and decision-making in AD. For example, early signs
of AD include both deficits in judgment, which may reflect changes to brain circuitry necessary for
behavioral flexibility and difficulties in familiar tasks, which may reflect changes in brain circuitry
necessary for habitual control of behavior. For this supplement, we propose to characterize the
neural signaling changes in the Transgenic AD rat (TgF344-AD) in the corticostriatal pathways
during behavioral flexibility. Specifically, similar to the parent grant we will explore the medial
prefrontal cortex subregions (prelimbic and infralimbic) linked to ventral (i.e., nucleus accumbens)
and dorsal striatum subregions. We will also link alterations in neurophysiology and behavioral
to neurochemical and histopathological changes in AD rats. Data obtained through this
administrative supplemental mechanism will drive future studies and grant applications that will
examine how alterations in neurophysiology in corticostrial circuits link to behavior to more
accurately predict the progression of AD, and in combination with the parent award, how drugs of
abuse affect this progression.

## Key facts

- **NIH application ID:** 10121211
- **Project number:** 3R00DA042934-03S1
- **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:** $309,426
- **Award type:** 3
- **Project period:** 2017-09-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10121211

## Citation

> US National Institutes of Health, RePORTER application 10121211, NEURAL CIRCUITRY MEDIATING BEHAVIORAL FLEXIBILITY (3R00DA042934-03S1). Retrieved via AI Analytics 2026-05-31 from https://api.ai-analytics.org/grant/nih/10121211. Licensed CC0.

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