# Dynamics of cortico-limbic circuit function during naturalistic risky decision-making in a mouse model of Alzheimer's disease

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2020 · $409,889

## Abstract

PROJECT SUMMARY
The natural process of aging is also the leading risk factor for Alzheimer’s disease (AD), a prevalent form of
dementia that has devastating effects on the quality of human life and health care costs. As cognitive functions
progressively deteriorate with AD, a neurobiological understanding of how AD alters brain cells and their circuit
functions is one of the great challenges facing modern biomedical research with broad implications for
advancing the nation’s health as well as stimulating the economy. Considerable human and animal AD
research has focused on relating ‘physical’ (macroscopic, microscopic) changes in the brain with destructive
loss of memory (i.e., anterograde and retrograde amnesias). In contrast, significantly less is known about the
impact of AD on other cognitive functioning, such as risky decision-making which plays pervasive role in daily
life, and how AD-afflicted neurons operate in ‘real-time’ as cognitive functioning is taking place. The primary
goal of this application is to understand the dynamics of prelimbic cortex-hippocampus (PL-HPC) circuit
functions in decision-making in a murine model of AD, utilizing an ecologically-relevant behavioral paradigm.
We will test the general hypothesis that AD causes coordinated PL-HPC neural activities and risky decision-
making abilities to decline as a function of the amyloid plaque accumulation in the two structures. There are
two specific aims of the project: (1) an ETHOBEHAVIORAL ANALYSIS will investigate the scope of amyloid plaque
effects on the animal’s ability to discern safety-danger boundary and make optimal risky foraging decisions;
and (2) a SYSTEMS-LEVEL ANALYSIS will determine the neural synchrony in the PL-HPC network as AD mice
perform risky foraging and also probe whether decision-making deficits can be alleviated by optogenetic
intervention. Information generated from this project would be of significance (1) from a basic scientific
perspective because it will provide novel data pertaining to AD-associated changes neural coding and
decision-making; and (2) from an applied perspective because it provides a new avenue of naturalistic-based
preclinical research that can potentially lead to developing successful treatments of AD-related declines in
cognitive functions.

## Key facts

- **NIH application ID:** 9951981
- **Project number:** 1R21AG067008-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Eun Joo Kim
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,889
- **Award type:** 1
- **Project period:** 2020-05-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9951981

## Citation

> US National Institutes of Health, RePORTER application 9951981, Dynamics of cortico-limbic circuit function during naturalistic risky decision-making in a mouse model of Alzheimer's disease (1R21AG067008-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9951981. Licensed CC0.

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