# Cortical Astrocyte - Neuronal Network Pathophysiology in Alzheimer's Disease In Vivo

> **NIH NIH F31** · UNIVERSITY OF MINNESOTA · 2020 · $40,088

## Abstract

Cortical activity underlying cognitive function is classically thought to be exclusively mediated by neurons. In
contrast, astrocytes are considered to play solely homeostatic roles, without being directly involved in brain
function. Yet, astrocytes are emerging as important cells in brain physiology because they interact with neurons
establishing Tripartite Synapses, responding to neurotransmitters with rises in internal calcium levels leading to
the release of gliotransmitters that regulate synaptic function. While astrocyte calcium and consequent synaptic
regulation has been largely documented at the single cell level, astrocyte network activity and its impact on
neuronal network function has been minimally explored. Through the dysregulation of this interaction, astrocytes
may be involved in brain pathology, contributing 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 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 loss or damage of synapses. Beta-amyloid pathology has
been shown to disrupt cortical astrocyte calcium homeostasis and desynchronize neuronal networks, however
disturbances caused by astrocyte-neuron dysfunctions on evoked cortical activity in AD remain unknown. The
overall goal of this proposal is to identify astrocyte cortical activity, its impact on neuronal network function, and
beta-amyloid induced dysregulation of astrocyte-neuron interactions in AD. To assess astrocyte impact on
neuronal network function, I will monitor astrocyte calcium activity using two-photon microscopy simultaneously
with ECoG recordings of neuronal network activity in vivo. While monitoring the somatosensory cortex during
hind-paw stimulation, I will test the hypothesis that cortical astrocytes respond to sensory stimulation, they impact
neuronal network activity, and astrocyte-neuron interactions are altered in AD. I will begin by identifying cortical
astrocyte calcium activity in response to sensory stimulation (Aim 1a). Due to its overexpression of beta-amyloid,
I will use the well-established APP/PS1 mouse model of AD to evaluate the impact of Aβ plaques on cortical
astrocyte responsiveness to sensory stimulation (Aim 1b). I will then monitor astrocyte calcium simultaneously
with neuronal network function during sensory stimulation to identify coordination of neuron – astrocyte network
activity (Aim 2a). Finally, I will monitor astrocyte calcium and neuronal network activity in the APP/PS1 mouse
model to assess alterations in neuron – astrocyte interactions by beta-amyloid in AD (Aim 2b). This project will
aid in the elucidation of novel cellular and network dynamics that are disrupted in Alzheimer’s disease, and
provide new potential therapeutic targets for the treatment of Alzheimer’s disease. Astrocyte calcium ...

## Key facts

- **NIH application ID:** 9849124
- **Project number:** 5F31AG057155-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Justin Lines
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,088
- **Award type:** 5
- **Project period:** 2018-12-24 → 2020-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849124

## Citation

> US National Institutes of Health, RePORTER application 9849124, Cortical Astrocyte - Neuronal Network Pathophysiology in Alzheimer's Disease In Vivo (5F31AG057155-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9849124. Licensed CC0.

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