# Deciphering aging-driven cognitive decline in C. elegans spatial memory and learning through an interdisciplinary approach

> **NIH NIH K01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $120,540

## Abstract

Project Summary
Cognitive decline is a central issue in neurobiology of aging, not only due to its profound scientific interest, but
also because people with mild cognitive impairment are at increased risk of developing Alzheimer's or another
dementia. Even though human cognition may differ from animal cognition, cognitive behaviors like memory,
learning, decision making and environmental information processing are widely observed even in invertebrate
animals. C. elegans nematode is an exemplary model organism in both biology of aging and neurobiology.
Cognitive behaviors (memory, learning and decision making) are being steadily clarified using C. elegans
worms, mainly however in the context of chemical stimuli; hence little is known about their cognitive aging in
relation to spatial navigation. Still, the need for elucidating the cellular and molecular details of these processes
remains pressing. The emerging potential of C. elegans as model system for behavioral and cognitive studies
could significantly help the scientific community understand aging-driven cognitive decline and its mechanisms
in higher organisms, including humans. The proposed research focuses on characterizing aging-driven
cognitive decline. We hypothesize that normal aging differentially affects multiple cognitive functions, and that
specific neurons and neuronal circuits are more susceptible to aging effects, functioning as "aging hubs" that
determine the performance of entire networks. To test this, we have planned two research thrusts, one
experimental and one computational. We will use a custom-made cognitive aging studying platform for worms,
i.e. the Worm-Maze. To characterize aging-driven cognitive decline, we will investigate the impact of aging on
spatial memory and on decision making under conflicting environmental cues. Next, we will genetically
inactivate selected neurons by silencing target genes, to identify genes and neurons that govern these
behaviors and we will detect how each of them is affected by aging. Live calcium imaging will be used to track
firing neurons. For the computational part, we will build mathematical models to describe learning, spatial
memory and decision making, and predict the performance of neuronal networks undergoing aging. Thus, by
combining experimental and computational efforts, we will identify "aging hubs" in the cognition-related
neuronal networks. Successful outcome of the proposed work will significantly contribute to understanding
aging of neuronal circuits involved in cognition. The proposed research plan is based on the applicant's strong
background in neurobiology and her engineering experience. Together with the career plan, they aim to
strengthen and expand the applicant's knowledge in genetics, behavioral studies and computational
neuroscience in order for her to grow into a uniquely positioned independent investigator in contemporary
neurobiology of aging. Well rounded career development through targeted research activ...

## Key facts

- **NIH application ID:** 10135802
- **Project number:** 5K01AG057833-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Eleni Gourgou
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $120,540
- **Award type:** 5
- **Project period:** 2018-07-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135802

## Citation

> US National Institutes of Health, RePORTER application 10135802, Deciphering aging-driven cognitive decline in C. elegans spatial memory and learning through an interdisciplinary approach (5K01AG057833-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135802. Licensed CC0.

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