# Holographic activation of ensemble activity during sleep in a mouse model of Alzheimer's disease

> **NIH NIH K99** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $132,705

## Abstract

Alzheimer’s disease (AD) affects more than 5.8 million elderly adults and is the most fatal
dementia in the US. Patients diagnosed with AD present with cognitive decline including a loss in
long-term memory. Perceptual memory is encoded on the synchronous firing of cells within a
cortical network, and ensemble activity can be recalled with sensory cues, or it can be reactivated
spontaneously during sleep. During sleep, the brain is placed in a quiescent state of slow-wave
activity, where recently acquired memories are believed to spontaneously reactivate in order to
consolidate into long-term storage. Human AD patients show memory deficits along with poor and
fragmented sleep. Due to impairments in long term memory and sleep in AD patients and animal
models, it is theorized that memory reactivation may also be impaired in AD. At this point memory
reactivation has not been studied during sleep in AD. Animal studies where memory reactivation
is artificially disrupted show memory deficits, and interestingly, animal research has demonstrated
that spurring additional memory reactivation during sleep can improve memory consolidation.
Interestingly, even the introduction of auditory stimulation to enhance slow-wave activity during
sleep has been shown to aid the retention of new memories. In a recent study, stimulating slow-
wave activity during sleep in human patients with mild cognitive impairments led to increases in
memory retention. The overall goal of this proposal is to gauge memory reactivation in a mouse
model of Alzheimer’s disease and to stimulate memory reactivation during sleep in AD mice to
increase memory performance. I will use two-photon microscopy in parallel with recordings of
electrophysiology to measure brain activity across wake and sleep. AD model animals will be
imaged during sleep following a learning task to test the hypothesis that memory reactivation is
impaired in an AD mouse model (Aim 1). In a separate set of experiments, the stimulation of virally
delivered opsins will be used to spur additional memory reactivation in sleep following a learning
task to test the hypothesis that spurring memory reactivation during sleep will improve memory in
a mouse model of AD (Aim 2). The conclusion of this project will determine the specific alterations
in memory reactivation during sleep contributing to memory deficits found in an AD mouse model,
and identify the potential to modulate network activity during sleep to rescue memory deficits in a
mouse model of AD. The completion of this preclinical research may influence early diagnosis of
AD and lead to innovations of novel therapeutics for AD. Through the completion of this project, I
will be exposed to training in optical techniques, electrophysiology, behavior, and sleep science
in preclinical animal models to become an independent research scientist.

## Key facts

- **NIH application ID:** 10785393
- **Project number:** 1K99AG084853-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Justin Lines
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $132,705
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10785393

## Citation

> US National Institutes of Health, RePORTER application 10785393, Holographic activation of ensemble activity during sleep in a mouse model of Alzheimer's disease (1K99AG084853-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10785393. Licensed CC0.

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