# The role of the locus coeruleus in vagus nerve stimulation effects on age-related memory deficits

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2022 · $203,125

## Abstract

PROJECT SUMMARY/ABSTRACT
Certain memory deficits are a natural part of healthy aging but can be severe in numerous age-related brain
disorders, including Alzheimer's Disease (AD). Given the devastating effects that these deficits can have on
patients and their families, plus the fact that our population is aging, there is an urgent need to identify new
approaches to combat age- and disease-related memory deficits. One promising potential approach uses
vagus nerve stimulation (VNS), which is thought to enhance memory abilities via activation of the locus
coeruleus (LC)-norepinephrine (NE) system. However, exactly how VNS affects the LC-NE system, and how
those effects relate to memory enhancements, is not well understood, particularly in the primate brain. This
knowledge gap is problematic because the LC is one of the first brain regions to degrade in AD and more
generally tends to decline in size and neuron number with aging. Thus, establishing VNS as a viable treatment
for age- and AD-related memory deficits requires first understanding its dependence on the intact and
potentially degraded LC. The goal of this study is to establish a new understanding of how VNS affects
memory via LC-NE activation in younger and older primate brains, using rhesus monkeys as a model system
for probing the underlying mechanisms in detail. To achieve this goal, we pair VNS with neural recordings in
LC and first focus on identifying patterns of VNS (e.g., with respect to timing, frequency, and duration of
stimulation) that most effectively activate LC. We then use VNS combined with LC recordings in monkeys while
they perform the Mnemonic Similarity task, a visual memory task demonstrated in humans to differentiate
individuals with mild cognitive impairment and AD from other forms of decline. We pursue two specific Aims.
For Aim one, we relate VNS-induced changes in LC neural activation patterns to memory performance in
adolescent (age 5–10 yr) rhesus monkeys. For Aim two, we relate VNS-induced changes in neural activation
patterns to memory performance in older (age 18–23 yr) rhesus monkeys. Together these Aims will provide
mechanistic insights into how VNS can enhance memory via LC and cortical activation patterns in both young
and old primate brains. The results will support future development of VNS as a treatment for memory deficits
in age-related diseases including AD.

## Key facts

- **NIH application ID:** 10469695
- **Project number:** 5R21AG074047-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** JOSHUA I GOLD
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $203,125
- **Award type:** 5
- **Project period:** 2021-08-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469695

## Citation

> US National Institutes of Health, RePORTER application 10469695, The role of the locus coeruleus in vagus nerve stimulation effects on age-related memory deficits (5R21AG074047-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10469695. Licensed CC0.

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