# A mouse model of cognitive reserve and its effects on memory related hippocampal coding dynamics in healthy and Azheimer's mice

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $428,538

## Abstract

For a given age or level of brain pathology, patients with higher educational status, occupational achievement,
bilinguality, and school grades show fewer symptoms of dementia. Such factors have been lumped into a
concept called “Cognitive Reserve” (CR), which is the principal correlate of resilience against dementia and
normal, age-related cognitive decline. CR “may be based on more efficient utilization of brain networks or of
enhanced ability to recruit alternate brain networks", or it may reflect intrinsic (innate) brain physiology
differences; however, evidence indicates a major role of the degree of knowledge acquisition over the lifespan.
But the linkages between enhanced experience and CR, and between CR and neurobiological function, need
to be experimentally established. Does enhanced experience actually create CR? What are the neurobiological
correlates of CR? Does CR actually preserve neurobiological function, such as the ability to retrieve recent
activity patterns or the ability to rearrange synaptic connections, or is it merely a reflection of the complexity of
patterns stored before the onset of brain pathology? As an animal proxy for CR, we will exploit a new method
for environmental enrichment that we have developed, which produces striking improvements in at least five
different tests of memory and cognitive function in normal mice. These improvements are significantly superior
to classical environmental enrichment methods, allow for tight control of enrichment parameters and exercise
variables, and last at least 6 months. Using advanced optical cellular activity imaging in freely behaving mice
and neural ensemble recording methods in a VR apparatus we will assess the neurodynamic effects of EE in
the hippocampus of normal mice and in an animal model of Alzheimer's disease (AD). We will study a range of
hippocampal neurodynamics that are believed to reflect or to play a key role in memory processes. These
parameters include hippocampal oscillations such as theta rhythm and sharp-wave-ripples (SWR), `place' cell
population coding of environmental location, rate coding of changes in external inputs at a given location (“rate-
remapping”), experience-dependent encoding of sequential experience, representational efficiency (sparse
coding, log-normal firing rate distributions) and temporal stability, and post experience reactivation of recent
memories during periods of rest. We will compare the effects of running the Enrichment Track with running on
an Exercise Control Track. Parallel studies of the effects of Enrichment Track and Control Track on
amelioration of cognitive/behavioral deficits in the same, 3xTg AD, mice are being conducted under separate
support, which will enable us to assess which neural dynamic parameters best account for behavioral
improvements and set the parameters for future within-subject experiments that would enable direct correlation
and manipulation. CR is a significant factor not only in protection of cog...

## Key facts

- **NIH application ID:** 9958851
- **Project number:** 1R21AG067052-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** BRUCE L MCNAUGHTON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $428,538
- **Award type:** 1
- **Project period:** 2020-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9958851

## Citation

> US National Institutes of Health, RePORTER application 9958851, A mouse model of cognitive reserve and its effects on memory related hippocampal coding dynamics in healthy and Azheimer's mice (1R21AG067052-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9958851. Licensed CC0.

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