ORCID ID

https://orcid.org/0000-0003-3793-5283

Publication Date

2021-04-28

Document Type

Doctoral Dissertation

Academic Program

MD/PhD

Department

Neurobiology; Anaclet Lab

First Thesis Advisor

Christelle Anaclet, PhD

Keywords

Slow-wave-Sleep enhancement, Hippocampus-dependent memory, Aging, Alzheimer's Disease, APP/PS1 mice, Mouse Models, Slow Wave Activity, Chemogenetics, Behaviour

Abstract

Aging and Alzheimer’s disease (AD), are associated with disabling sleep and cognitive deficits. Specifically, aging and Alzheimer’s disease is associated with reduced quantity and quality of the deepest stage of sleep, called slow-wave-sleep (SWS). Interestingly, SWS has been implicated in hippocampus-dependent memory in mice. More importantly, sleep deprivation, aging, and AD are all associated with deficits in memory. Therefore, I hypothesize that, in aging and AD, the sleep deficits are, at least in part, responsible for memory impairments and increasing the quantity and quality of SWS will reverse these memory deficits.

I first developed mouse models of SWS enhancement in aging and AD. Chemogenetic activation of the parafacial zone GABAergic neurons enhances SWS in aged mice as previously described in adult mice. Similarly, in AD mice, SWS enhancement is as effective as in littermate wild-type controls. Then, I used these mouse models to characterize the role of SWS in memory using novel gain-of-sleep experiments. I found that acute SWS enhancement: 1) reduce spatial memory in adult mice and 2) failed to improve spatial memory in aged mice. In a preliminary study, acute SWS enhancement seems to improve contextual memory in AD mice.

Collectively, my work provides a novel mouse model of SWS enhancement in aging and AD, offering a pivotal tool to study the role of SWS in physiological functions and neurodegenerative diseases. Furthermore, my results suggest that acute SWS enhancement does not benefit the behavioral manifestation of memory consolidation in adult mice and aged mice.

DOI

10.13028/r1sq-wq38

Rights and Permissions

Copyright is held by the author, with all rights reserved.

Available for download on Friday, May 26, 2023

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