# Population Network Responses in AD Model Animals

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $205,000

## Abstract

Project Summary
In Alzheimer’s disease (AD), the first signs of cognitive impairment are observed many years before
a clinical AD diagnosis is established, and the loss of synaptic function in AD is evident long before
any substantial loss of neurons. The excessive production or accumulation of β-amyloid peptide
(Aβ) has been documented to have deleterious effects on synaptic activity by various mechanisms.
Understanding the cellular and molecular mechanisms of the early AD-associated synaptic
dysfunction (before the behavioral manifestations of severe learning and memory deficits) may be
critical for the development of new therapies for slowing down the progression of AD. However,
detection of the AD-associated changes in synaptic function among cortical circuits is technically
challenging, especially so if it is needed in the earliest stages of the AD process, before the
formation of plaques and tangles, when changes are small and difficult to spot. Where exactly, at
which cortical layer, or which synapse, one should investigate? The current assays for detecting
neural circuit deficiencies in AD model animals are based on traditional electrode electrophysiology
and have several practical limitations including: poor spatial resolution, blindness for cell-types, and
a labor intensive nature of experiments. New technologies bring an improved temporal and spatial
resolution for monitoring activity in many neurons simultaneously, thus facilitating studies on brain
circuitry disruptions in neurological disorders. We propose to use GEVI imaging (multi-cell optical
imaging of the membrane potential changes using genetically-encoded voltage indicators). Our
hypothesis is that “synaptic and neuronal dysfunctions emerge before significant Aβ deposition and
pathological tau aggregation, and can be routinely detected by affordable imaging methods”. A
simple and sensitive physiological assay for detecting changes in network physiology, prior to the
substantial accumulation of the amyloid plaques or reproducible behavioral deficits in learning and
memory, would accelerate the investigations of the earliest cellular and molecular changes
mediated by the AD pathological process. Understanding the cellular and molecular mechanisms of
the early AD-associated synaptic dysfunction (before the behavioral manifestations of the learning
and memory deficits) may help the development of the new therapies for slowing down the
progression of the AD.

## Key facts

- **NIH application ID:** 10263296
- **Project number:** 5R21AG064554-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** SRDJAN D ANTIC
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $205,000
- **Award type:** 5
- **Project period:** 2020-09-30 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10263296

## Citation

> US National Institutes of Health, RePORTER application 10263296, Population Network Responses in AD Model Animals (5R21AG064554-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10263296. Licensed CC0.

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