# Admin Supp: CRCNS: Unsupervised Learning of Hippocampal Sequence Dynamic in Sleep

> **NIH NIH R01** · RICE UNIVERSITY · 2022 · $401,998

## Abstract

Abstract:
Cognitive and memory deficits are debilitating features of Alzheimer's disease (AD) and related
dementias (ADRD), with devastating impacts on the quality of life for the unfortunately affected.
Of the cognitive domains that show early decline in AD/ADRDs, spatial memory is particularly
sensitive to impairment, which leads to long-term disability as well as loss of independence
causing not only enormous individual suffering but also significant socioeconomic cost for the
afflicted and their families. Recent research has pointed to the locus coeruleus as a region in
which early tau pathology first emerges. This can then spread transynaptically to efferent
regions and notably to the hippocampus, which receives prominent input from the LC. Thus, LC
tau pathology could precede widespread neuropathology in AD and ADRD. Given the prominent
role of the LC in maintaining arousal and normal sleep-wake patterns, alongside its strong
projections to the hippocampus, it is important to investigate the impact of tau pathology in the
LC region on network function in other brain regions important for memory and cognition. Our
parent grant is aimed at uncovering the sequential structure in the spiking activity of large
populations of hippocampal neurons during sharp-wave ripples and examining the dynamics of
these sequences across the course of sleep and waking. There is strong evidence directly
linking these activity patterns to memory storage and retrieval alongside important cognitive
processes, such as planning and episodic simulation. Yet, while the impact of AD and ADRD on
memory loss and dysfunction are well-know and have been linked with increased disturbances
during sleep, their effects on network activity patterns across sleep and waking that mediate
normal function remain largely unknown. In this supplement, we propose to measure and
evaluate the dynamics of hippocampal neuronal activities during behavior and subsequent sleep
in rats in a novel rodent model of ADRD-related pathology, where wild-type human tau is
over-expressed specifically in the locus coeruleus. The proposed experiments are an
extension of those to be performed under the parent grant and involve deployment of the same
set of analytical tools to test our hypothesis that tau-aggregation in the LC will reduce the
flexible restructuring of hippocampal neuronal spike patterns across sleep and waking.
This proposal will also initiate a new collaboration between the Kemere and Diba labs with Dr.
Sara Burke, an expert in animal models of AD and ADRD and aging, to characterize an
important animal model for these disorders. We expect that these studies will significantly
further understanding of how tauopathy-related dementias impacts hippocampal network
functions that serve in memory and cognition, and help to identify potential therapeutic
targets for future treatment.

## Key facts

- **NIH application ID:** 10499765
- **Project number:** 3R01NS115233-04S2
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** KAMRAN DIBA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $401,998
- **Award type:** 3
- **Project period:** 2019-08-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499765

## Citation

> US National Institutes of Health, RePORTER application 10499765, Admin Supp: CRCNS: Unsupervised Learning of Hippocampal Sequence Dynamic in Sleep (3R01NS115233-04S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499765. Licensed CC0.

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