# Pacing hippocampus sharp waves

> **NIH NIH R03** · GEORGETOWN UNIVERSITY · 2020 · $77,750

## Abstract

Abstract
 The sharp-wave ripple (SWR) is a neuronal activity spontaneously occur in the hippocampus. During
each SWR, neuronal assemblies coding animals’ experiences are reactivated in a temporally compressed
manner. This compressed replay is critical for the consolidation of episodic memory. SWRs occur thousands of
times every hour, during sleep and quiet restfulness. The occurrence rate reduces with aging and after
hippocampal damage resulting from Alzheimer’s disease (AD) and other neurodegenerative conditions.
Reduced SWR occurrence rate and quality may contribute to the impairment of memory consolidation of recent
experiences. We propose to use “pacing” (micro-electric shocks at a given rate) to prime the occurrence of
SWRs, and to examine whether pacing SWR can improve spatial memory of Alzheimer animal models.
 Two Specific Aims are proposed: Aim 1 To achieve minimally invasive pacing in free-moving animals
through wireless stimulation via an electrode placed in the lateral ventricles, outside of the hippocampus tissue.
Preliminary results have demonstrated that SWRs can be induced by non-contact stimulation, by weak electrical
field affecting the CA3 tissue in hippocampal slices. Experiments under Aim 1 will extend the preliminary results
from brain slice to whole animals, establishing an electrical-field stimulation in lateral ventricle. Aim 2 To test if
“artificial SWRs” induced by pacing can contribute to memory consolidation. We will also test if pacing can
improve memory consolidation in AD model (Tg2567) animals. These animals develop significant deficits in
spatial memory at 6-8 months of age. We will test if pacing can improve spatial memory in behavioral tests.
 Deterioration of hippocampus-dependent episodic memory is a hallmark of Alzheimer dementia and other
brain degeneration conditions. The proposal will be a first step in develop a therapeutic strategy for improving
memory with a non-pharmaceutical method, and less invasive than deep brain stimulation.

## Key facts

- **NIH application ID:** 9985708
- **Project number:** 5R03AG061645-02
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Jian-Young Wu
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $77,750
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985708

## Citation

> US National Institutes of Health, RePORTER application 9985708, Pacing hippocampus sharp waves (5R03AG061645-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9985708. Licensed CC0.

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