# Cognition & Hippocampal/Cortical Systems in Aging

> **NIH NIH P01** · JOHNS HOPKINS UNIVERSITY · 2024 · $80,723

## Abstract

This research program represents a multidisciplinary, integrated approach to understanding the effects of
normal aging on a critical brain system that supports cognitive functions affected in humans as they age. We
focus on brain aging in hippocampal/cortical circuits using Long Evans rats, an outbred strain that exhibits
individual differences in aging outcomes in well-characterized cognitive assessments. At older ages (24-26
month) cognitive impairment affects 50-60% of healthy male rats in this population, while the remaining aged
cohorts fall within the range of young adults (4-6 months). Research under this mechanism of support has
identified alterations in the brain that are tightly coupled to these cognitive outcomes, including the deleterious
effects of heightened neural activity in specific hippocampal circuits on memory function in aging. The current
proposal will include a direct comparison of individual differnces in neurocognitive aging in both male and
female outbred Long Evans rats (Core B). Our proposed plans will build on our achievements to leverage new
findings that will advance understanding of episodic memory in basic research with application to clinical
problems in aging. Our research program to date has translated successfully in studies of human aging. Now
in reverse-translation we will examine the homeostatic control of network/circuit function by a mechanism that
clinical studies have implicated in late-life cognitive outcomes as well as in risk and resilience for late-onset
AD; Its failure across the spectrum of aging/AD in the human brain is closely tied to cognitive impairment. Our
studies on homeostasis regulated by NPTX2/GluA4 will provide the first systematic basic research in aging
focused on hippocampal circuitry where loss of inhibitory control has been identified in the condition of
impairment in the Long Evans model. Further studies, including those on NPTX2/PV-interneurons will focus on
evidence for an augmentation of inhibition in aged rats with preserved cognitive function, relative to young
adults. We are testing the functional significance of that condition as serving a potential role in adaptive aging
to maintain excitatory/inhibitory balance and cognitive performance. New tools and methods for the study of
brain aging will advance the overall research program together with direct comparisons for individual
differences in aged female and male rats. To that end, three Cores (Administrative, Animal Resource, and
Bioinformatics/Data Management) will serve all of the participating investigators conducting research in the
four proposed projects.

## Key facts

- **NIH application ID:** 11076151
- **Project number:** 3P01AG009973-29S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Michela Gallagher
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $80,723
- **Award type:** 3
- **Project period:** 1997-09-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11076151

## Citation

> US National Institutes of Health, RePORTER application 11076151, Cognition & Hippocampal/Cortical Systems in Aging (3P01AG009973-29S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11076151. Licensed CC0.

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