# Neuronal Activity in Sleep & Wake in Alzheimer's Disease Mice

> **NIH NIH R21** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $189,000

## Abstract

The deep-brain imaging approach (microendoscopy) is a high throughput method that identifies
the temporal and spatial pattern of activity in specific phenotypes of neurons. We have hypothesized that
activity in small networks can identify normal versus diseased brains. To test this hypothesis, we will use
the two-wavelength miniscope to image activity of a subset of neurons in 5xFAD mice, a validated animal
model of Alzheimer’s disease (normal versus the homozygous littermates). We have created promoter-
driven calcium sensor that drives the red-shifted calcium indicator, jRGECO, into orexin-arousal
neurons. A separate calcium sensor (GCaMP6m) in GABA sleep neurons will be used as comparison.
The advantage of imaging neurons with two different wavelengths is that it allows for comparison of
arousal versus sleep neurons as the brain transitions between wake and sleep. We will image activity of
neurons that contain jRGECO and GCaMP during normal wake-sleep bouts and after 6h sleep loss. We
hypothesize that there is an abnormal temporal pattern of fluorescence during the transition from wake
to sleep in the brains of 5xFAD mice, and it worsens with progression of disease. This may explain the
cause of the disrupted sleep-wake patterns in Alzheimer’s disease. We hypothesize that abnormal activity
in deep brain circuits regulating sleep is a harbinger of disease. The overall impact of this small budget
project is that it will identify activity of two different juxtapositioned neurons during wake, NREM and
REM sleep in wildtype versus a disease model, which will aid in understanding how small clusters of
neurons behave as the waking brain falls asleep.

## Key facts

- **NIH application ID:** 10909336
- **Project number:** 5R21AG083236-02
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Priyattam J. Shiromani
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $189,000
- **Award type:** 5
- **Project period:** 2023-09-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909336

## Citation

> US National Institutes of Health, RePORTER application 10909336, Neuronal Activity in Sleep & Wake in Alzheimer's Disease Mice (5R21AG083236-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10909336. Licensed CC0.

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