# Abnormal spatial memory processing in tau pathology and neurodegeneration

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $396,250

## Abstract

Abstract
Tau pathology, including tau protein hyperphosphorylation, neurofibrillary tangles and subsequent
neurodegeneration, plays a key role in cognitive symptoms of tauopathies including Alzheimer’s disease.
Recent studies using animal models have made rapid progress in understanding tau pathogenesis and its
involvement in cognitive deficits. However, behavioral deficits are ultimately mediated by functional changes in
neural circuits in vivo. An important question that has rarely been studied is how neural circuit functions are
altered in the living brain with ongoing tau pathology and neurodegeneration. Here we propose to determine in
vivo functional abnormalities caused by tau pathology and neurodegeneration in the neural circuits of
hippocampus (HP) and entorhinal cortex, areas that are crucial for memory loss in tauopathies. Primarily using
the tetrode recording technique, in combination with behavioral and pharmacological manipulations, we will
simultaneously record a large number of neurons in freely moving animals of tauopathy mouse models,
including the transgenic rTg4510 mouse and htau mouse. We will focus on a specific “internal-external
imbalance” hypothesis: The memory circuits in these mice cannot form normal memories because they are
dominated by internal activities generated within the hippocampus and thus fail to respond to external sensory
input. To test the hypothesis, we will aim to determine whether activities of HP neurons in tauopathy models
are preferentially driven by internal activities more than those in control mice, how this abnormality is
generated by the memory neural circuits, what computational process it alters, and how it is linked to
behavioral memory deficits.

## Key facts

- **NIH application ID:** 9987766
- **Project number:** 5R01NS097764-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Daoyun Ji
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,250
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987766

## Citation

> US National Institutes of Health, RePORTER application 9987766, Abnormal spatial memory processing in tau pathology and neurodegeneration (5R01NS097764-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9987766. Licensed CC0.

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