# Neural activity underlying rapid behavioral recovery after blood flow improvement in Alzheimer mouse models

> **NIH NIH R21** · CORNELL UNIVERSITY · 2020 · $423,231

## Abstract

Summary
Blood flow in the brain of Alzheimer disease patients is substantially decreased as compared to age-matched
healthy controls. Recently, it was found that blood flow in Alzheimer’s disease mouse models is reduced
because neutrophils plug up capillaries resulting in a small, but impactful number of stalled capillaries.
Removing these plugs by interfering with neutrophil adhesion improves blood flow in minutes and also
improves performance on tasks involving short term or episodic memory within hours. This extremely rapid
change in cognitive performance suggests that no alterations in structure or connectivity of neurons are
needed to recover sizable amounts of cognitive function in Alzheimer disease. Instead, there must be a change
in the neural activity that reflects the improvement in function. This phenomena enables the investigation of
these changing activity patterns by recording from the same cells before and after improving the blood flow.
Cutting-edge approaches, such as multiphoton microscopy of genetically encoded calcium indicators, will be
used to record activity from numbers of neurons deep inside the brain while still resolving individual cells in an
awake animal. Neurons with aberrant activity may underlie the observed cognitive deficits will be identified by
measuring how the activity in each cell changes before and after the blood flow treatment that rescues
cognition. This gives a direct measurement of how individual neurons and circuits change when an Alzheimer
mouse’s cognitive symptoms are improved. Several types of aberrant neural activity are known to be
associated with Alzheimer’s disease and also with impaired blood flow, suggesting that these types of neural
activity patterns might change during blood flow rescue. Studies in Alzheimer disease models show some
neurons are abnormally quiet or silent and other neurons fire spontaneously at excessively high rates. Imaging
of neural activity is used to evaluated changes in such activity in the hours and days after blood flow rescue.
Such aberrant firing patterns can contribute to a decrease in the accuracy of neural representations of stimuli.
Neural fidelity is assayed by measuring tuning curves in neurons that respond to directional whisker
stimulation. Imaging of somatosensory cortex tests whether blood flow rescue improves these tuning curves
and sensitivity to weak stimuli. Alzheimer’s disease patients and experimental models exhibit seizure-like
discharges, so EEG recording is used to evaluate epileptiform activity and any changes with blood flow rescue.
Interestingly, the blood-flow-mediated cognitive changes are so fast that there is little time for slower changes
such as rewiring of circuits. Understanding what are the changes that are caused by blood flow rescue that are
correlated with the fast behavioral improvement is critical to understanding how the cognitive symptoms emerge
in the disease. This work suggests that a metabolic component is critical to cogn...

## Key facts

- **NIH application ID:** 9877249
- **Project number:** 1R21AG066001-01
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Nozomi Nishimura
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,231
- **Award type:** 1
- **Project period:** 2020-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9877249

## Citation

> US National Institutes of Health, RePORTER application 9877249, Neural activity underlying rapid behavioral recovery after blood flow improvement in Alzheimer mouse models (1R21AG066001-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9877249. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*