# Non-Invasive Methods to Drive Neural Activity with Millisecond Precision and to Recruit the Brain’s Immune Cells

> **NIH NIH R01** · GEORGIA INSTITUTE OF TECHNOLOGY · 2022 · $333,367

## Abstract

Non-invasive methods to drive neural activity with millisecond precision and to recruit the brain's
immune cells
We recently discovered that flickering lights at gamma frequency (40 Hz) drives gamma frequency neural
activity in visual cortex and recruits microglia to engulf pathogenic proteins in mouse models of Alzheimer's
disease. However we do not yet know how to achieve these effects outside of visual cortex. If this sensory
stimulation method could be adapted to non-invasively drive neural activity in deep brain regions this novel
approach would enable new possible therapeutics for Alzheimer's and other neurological diseases. Our long-
term goal is to harness these novel discoveries in order to manipulate neural activity and immune cells in
humans. The goal of this proposal is to determine how to non-invasively drive temporally precise rhythmic
neural activity in deep brain structures and to determine the effects of driving this activity on immune cells,
synaptic plasticity, and neural codes essential for learning and memory in healthy mice and mouse models of
Alzheimer's disease. In Aim 1 we will determine what types of sensory flicker produce the strongest rhythmic
neural activity in deep brain structures. In Aim 2 we will establish the functional consequences of driving this
non-invasive stimulation on microglia, connections between neurons, and neural codes essential for learning
and memory. The rationale for this approach is that our discovery that millisecond precision sensory flicker
stimulation drives rhythmic neural activity and recruits microglia provides the foundation for an innovative new
method to non-invasively manipulate neural activity and immune cells. To achieve these aims, we will employ
two key innovations. First, we will leverage our recent discovery showing that 40 Hz sensory stimulation drives
gamma frequency activity and recruits microglia. Second, we will record neural activity in mice as they navigate
a virtual reality environment to record neural activity from many cells of multiple types during behavior. The
expected outcomes of these studies are novel non-invasive methods to drive neural activity, recruit immune
cells, and alter synaptic plasticity and neural codes in deep brain structures. Because rhythmic brain activity
and microglia are implicated in many neurological diseases and in learning and memory, these methods will
spur new clinical and basic science research with wide-ranging impact. The novel approaches used in the
study will be broadly distributed to drive further research on neural activity, immune cells, and neural-immune
interactions.

## Key facts

- **NIH application ID:** 10476302
- **Project number:** 5R01NS109226-05
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Annabelle Catherine Singer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $333,367
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-09-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10476302

## Citation

> US National Institutes of Health, RePORTER application 10476302, Non-Invasive Methods to Drive Neural Activity with Millisecond Precision and to Recruit the Brain’s Immune Cells (5R01NS109226-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10476302. Licensed CC0.

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