# Interneuron and Network Synchrony in Alzheimer's Disease

> **NIH NIH R03** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $93,540

## Abstract

Project Summary/Abstract
Alzheimer's disease (AD) is a form of dementia characterized by memory loss and progressive cognitive
impairments. Memory impairments in AD increase with age and are linked to hyperexcitability, interneuron
death, circuit remodeling, and impaired interneuron function. Interneuron loss and dysfunction are well
established in AD, yet it remains unclear how these anatomical changes contribute to cognitive deficits.
Interneurons play a critical role in synchronizing local networks to generate brain rhythms important for long-
term potentiation and memory encoding and interneuron loss has been associated with reduced oscillations
and memory impairments in AD models. Understanding how hippocampal interneurons are functionally altered
in AD, both before and after the emergence of learning impairments, is critical to understanding these cognitive
deficits. In this proposal, we will test the hypothesis that hippocampal interneuron synchrony is altered in AD
model mice, and that network dysfunction in young, pre-symptomatic mice can predict memory impairments.
To examine the relationship between interneuron activity and local networks, we will use silicon probes to
record simultaneously from local field potentials and single units throughout CA1 and dentate gyrus (DG) of
3xTg-AD and wild type mice running in virtual reality. We will first examine the firing patterns of interneurons in
6 month old AD model mice, after the onset of memory impairments. We hypothesize that interneurons in AD
model mice will have abnormal firing patterns relative to network oscillations, which will desynchronize
interneurons across CA1 and DG. Next, we will use young 3xTg-AD mice, prior to memory impairments, in
order to investigate whether specific network changes can predict future cognitive decline. We hypothesize that
alterations in network function (such as interneuron phase locking, oscillation power or coherence) will predict
the severity of memory impairments at a later time point. These experiments will highlight potential targets for
early therapeutic interventions and lead to new insights into the progression of memory impairments in AD.
Characterizing hippocampal desynchrony in AD and how it contributes to cognitive deficits will be critical in
developing targeted treatments for AD, especially preventative intervention during the pre-symptomatic phase
where success is most viable.

## Key facts

- **NIH application ID:** 10055564
- **Project number:** 3R03NS111493-01S2
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Tristan Shuman
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $93,540
- **Award type:** 3
- **Project period:** 2020-05-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10055564

## Citation

> US National Institutes of Health, RePORTER application 10055564, Interneuron and Network Synchrony in Alzheimer's Disease (3R03NS111493-01S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10055564. Licensed CC0.

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