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    The Role of Slow-Wave-Sleep in Hippocampus-Dependent Memory in Aging and Alzheimer's Disease

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    Authors
    Ogbeide-Latario, Oghomwen
    Faculty Advisor
    Christelle Anaclet, PhD
    Academic Program
    MD/PhD
    UMass Chan Affiliations
    Anaclet Lab
    Neurobiology
    Document Type
    Doctoral Dissertation
    Publication Date
    2021-04-28
    Keywords
    Slow-wave-Sleep enhancement
    Hippocampus-dependent memory
    Aging
    Alzheimer's Disease
    APP/PS1 mice
    Mouse Models
    Slow Wave Activity
    Chemogenetics
    Behaviour
    Behavioral Neurobiology
    Cognitive Neuroscience
    Neuroscience and Neurobiology
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    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
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/31366
    Rights
    Copyright is held by the author, with all rights reserved.
    ae974a485f413a2113503eed53cd6c53
    10.13028/r1sq-wq38
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    Morningside Graduate School of Biomedical Sciences Dissertations and Theses
    Neurobiology Student Publications

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