# Tracking the onset of spatial memory deficits in aging and Alzheimers disease models with single neuron resolution electrophysiology

> **NIH NIH K99** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $128,007

## Abstract

Project Summary/Abstract
 Aging changes the adult brain both structurally and functionally. Something about these changes
promotes cognitive decline and increases the risk of Alzheimer’s disease, a neurodegenerative disease that
affects millions of Americans and is the leading cause of dementia among adults. I propose to carry out
longitudinal electrophysiology and behavioral studies to understand how age-related changes in individual
neurons and their circuits contribute to cognitive impairments in mouse models of aging and Alzheimer’s disease.
I plan to take advantage of a novel biotechnology, mesh electronics, that will overcome many previous challenges
preventing the study of aging processes of single neurons and their circuits. I will use this technology combined
with behavioral tasks in virtual reality to understand how neurons and their circuits within the hippocampus and
entorhinal cortex change with normal aging and lead to cognitive decline. Then I will perform similar studies to
understand how spatial memory and learning deficits arise in a model of early aging in Alzheimer’s disease that
expresses pathological tau, with the goal of determining if either soluble or aggregated tau leads to neuronal
dysfunction and spatial memory impairment or if they arise coincidentally. These data will be extremely valuable
for the medical community as aggregated tau is currently the target of several ongoing clinical trials. These
experiments will also establish mesh electronics as a useful tool for the study of normal and pathological aging
that could be extended to understand the onset of cognitive decline in many other model systems.

## Key facts

- **NIH application ID:** 10040995
- **Project number:** 1K99AG068602-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Theodore Joseph Zwang
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $128,007
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10040995

## Citation

> US National Institutes of Health, RePORTER application 10040995, Tracking the onset of spatial memory deficits in aging and Alzheimers disease models with single neuron resolution electrophysiology (1K99AG068602-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10040995. Licensed CC0.

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