# Neural circuitry mediating behavioral flexibility

> **NIH NIH R00** · ROWAN UNIVERSITY SCHOOL/OSTEOPATHIC MED · 2022 · $268,277

## Abstract

Project Summary
Alzheimer’s disease (AD) is characterized by memory impairments and underlying neuropathology, including
plaques, amyloid-β peptides, tau, in conjunction with neuroinflammation, and neuronal injury/loss. Recent
studies suggest that alterations in neurophysiology are evident in patients with AD prior to gross neuropathology.
Given that the prefrontal cortex contributes to top-down control of memory processing necessary for optimal
decision-making, dysfunction within the PFC may contribute to suboptimal decision-making which often precedes
gross memory loss in AD patients. Optimal decision-making requires functioning behavioral flexibility (the ability
to shift behavior in response to changing consequences). The rat prelimbic cortex (PrL), and its connection with
the nucleus accumbens (NAc), is heavily implicated in behavioral flexibility as measured by the ability to shift
behavior after following outcome devaluation. The parent award is aimed to determine how a history of cocaine
alters the corticostriatal neural network signaling that drives impaired behavioral flexibility (i.e., post outcome
devaluation). We recently have found that transgenic AD rat (TgF344-AD) show impaired behavioral flexibility
in this task compared to wild type litter mate control rats. Critically, AD rats show aberrant neurophysiological
processing in the PrL to reward predictive cues. Specifically, PrL neuronal firing in the AD rats is hyper-
responsive to reward predictive cues following outcome devaluation (i.e., PrL neurons in AD rats increase their
firing rates to devalued reward predictive-cues where as PrL neurons in WT rats decrease firing rates to these
cues). This current administrative supplement will aim at examining how these aberrant neurophysiological
signatures are linked to impairments in behavioral flexibility. Specifically, we will utilize optogenetic techniques
to determine if increased PrL input into the NAc is causally linked to impaired expression of behavioral flexibility
in AD rats. Findings obtained through this supplement will allow for circuit level mechanistic insight into the AD
impaired expression of behavioral flexibility following changes in outcome value in order to guide future
therapeutics for impaired valued based decision-making in AD patients.

## Key facts

- **NIH application ID:** 10497958
- **Project number:** 3R00DA042934-05S2
- **Recipient organization:** ROWAN UNIVERSITY SCHOOL/OSTEOPATHIC MED
- **Principal Investigator:** Elizabeth A West
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $268,277
- **Award type:** 3
- **Project period:** 2020-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10497958

## Citation

> US National Institutes of Health, RePORTER application 10497958, Neural circuitry mediating behavioral flexibility (3R00DA042934-05S2). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10497958. Licensed CC0.

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