# Holographic reprogramming of memories during sleep in a mouse model of Alzheimers disease

> **NIH NIH F32** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2021 · $65,610

## Abstract

Cortical activity underlying perceptual memory is believed to occur in the organized firing of neuronal ensembles.
Memory formation can be decomposed into acquisition and consolidation processes, wherein information is
gained and stored respectively. Memory consolidation is thought to occur while we sleep, when the brain is in a
quiescent state to allow previously formed neuronal ensembles to reactivate. While memory reactivation and its
consequent role in consolidation has been largely documented, stimulating the replay of individual ensembles
during sleep to enhance memory outcomes has been only indirectly explored. Indeed, impairments to memory
reactivation alter memory consolidation and this may contribute to the cognitive deficits in neurodegenerative
diseases such as Alzheimer’s disease (AD). AD is the leading cause of dementia in the United States, and yet
the network mechanisms contributing to cognitive decline are unclear. The disease progression is associated
with depositions of senile plaques of beta amyloid (Aβ) aggregates as well as neurodegeneration. Beta amyloid
pathology has been shown to disrupt cortical homeostasis and desynchronize neuronal networks, however
disturbances caused by Aβ pathology on sleep-mediated memory reactivation remain unknown. The overall goal
of this proposal is to determine the role of memory reactivation on memory consolidation during sleep, as well
as characterize beta amyloid induced impairments in reactivation in a mouse model of amyloidosis. To assess
memory reactivation during sleep, I will monitor neuronal calcium activity from thousands of neurons using 3D
holographic two-photon microscopy simultaneously with local field potential recordings of neuronal network
activity in vivo. In order to stimulate specific ensemble activity, I will excite individual cells in previously observed
ensembles using holographic targeted optogenetics. While monitoring and stimulating the visual cortex during
sleep following a Go/No-Go set learning task, I will test the hypothesis that stimulating memory reactivation
during sleep will enhance memory consolidation, and memory reactivation is altered in a mouse model of AD. I
will begin by comparing neuronal ensemble stability following optogenetic stimulation across wake – sleep states
(Aim 1a). I will then monitor behavioral performance following targeted optogenetic stimulation across wake and
sleep to identify improvements in behavioral outcome (Aim 1b). Due to its overexpression of beta amyloid, I will
use the 5XFAD mouse model of AD to evaluate the impact of Aβ plaques on ensemble reactivation during sleep
(Aim 2a). Finally, I will monitor neuronal network activity and behavior in the 5XFAD mouse model to assess
cellular and behavioral enhancements following optogenetic targeted replay during sleep (Aim 2b). This project
will aid in the elucidation of sleep memory processing stages that may be disrupted by beta amyloid pathology,
and provide potential therapeutic ta...

## Key facts

- **NIH application ID:** 10152135
- **Project number:** 1F32AG069354-01A1
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** Justin Lines
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $65,610
- **Award type:** 1
- **Project period:** 2021-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152135

## Citation

> US National Institutes of Health, RePORTER application 10152135, Holographic reprogramming of memories during sleep in a mouse model of Alzheimers disease (1F32AG069354-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10152135. Licensed CC0.

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