# Circuit mechanisms underlying associative memory impairment in knock-in Alzheimer's model

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $43,854

## Abstract

Project Summary
Alzheimer’s disease (AD), the most common dementia, currently affects ~6 million individuals in the U.S. and is
expected to triple by 2050. A devastating hallmark symptom is the progressive loss of the ability to form
memories. Treatments for rescuing memory function in AD patients are nonexistent, due in part to insufficient
research characterizing the activity of neural memory circuits affected by AD. Developing memory-restoring
therapeutics that modulate specific neural circuits demands investigation of which circuit-level functions are
impacted, when during pathophysiological progression they show impairment, and how they relate to memory
performance. Neurons in the entorhinal cortex (EC) act as a gateway for sensory inputs feeding into the
hippocampus. This EC-hippocampus circuit is critical for memory formation and retrieval. The lateral entorhinal
cortex (LEC) is a primary site of atrophy and activity loss in the early phases of AD. Despite its significance to
AD pathophysiology, it remains unclear what type of activity is lost in the LEC of AD patients or animal models.
The proposed studies center on two Specific Aims: (Aim 1) Determine the time course of memory cell impairment
in APP-KI mice; and (Aim 2) Test whether reactivation of LEC dopamine inputs restores associative memory
formation. This study is expected to identify neuronal dysfunction of the LEC in AD. The project is expected to
yield advances towards developing therapeutics to rescue memory function via neuromodulation in the lateral
entorhinal cortex.

## Key facts

- **NIH application ID:** 10689059
- **Project number:** 5F31AG074650-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Jason Yen Sun Lee
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $43,854
- **Award type:** 5
- **Project period:** 2022-08-10 → 2024-08-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10689059

## Citation

> US National Institutes of Health, RePORTER application 10689059, Circuit mechanisms underlying associative memory impairment in knock-in Alzheimer's model (5F31AG074650-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10689059. Licensed CC0.

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