Dissertation
The molecular impact of sleep deprivation on the hippocampus
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2026
DOI: 10.25820/etd.008426
Abstract
Sleep deprivation (SD) disrupts brain cognitive functions, particularly hippocampus-dependent memory formation. Although the physiological consequences of SD on hippocampal circuits, such as impaired synaptic plasticity, have been widely documented, the molecular mechanisms underlying these changes remain incompletely understood. Previous studies have examined molecular responses to sleep loss using bulk hippocampal tissue or focused primarily on neuronal populations, limiting the resolution of subregion- and cell type-specific responses within hippocampal circuits. The goal of this thesis was to characterize the molecular impact of sleep deprivation on hippocampal neuronal population that actively engaged during sleep loss and non-neuronal cell populations.
Mapping activity across hippocampal subregions, indicated by immediate early gene c-Fos expression, revealed that SD non-uniformly activates excitatory neurons across hippocampal subregions, with CA1 exhibit the most prominent activity induction. To investigate molecular programs within SD-responsive neurons, an activity-driven ribosome-tagging (cFos-RiboTag) strategy was developed to selectively label SD-activated neurons and profile their translating mRNA. Using this cFos-RiboTag approach in combination with a repeated SD paradigm, a subset of CA1 pyramidal neurons was found to be preferentially reactivated across repeated SD episodes. Translatome analyses of these neurons revealed profound activity-dependent alterations in pathways associated with translation control, synaptic plasticity regulation, and insulin signalings.
To investigate non-neuronal contributions, single-nuclei RNA sequencing was performed on astrocytes and oligodendrocytes isolated from sleep deprived hippocampus. Astrocytes exhibited transcriptional altercations in pathways involved in cholesterol biosynthesis and mitochondrial functions, whereas oligodendrocytes showed changes in genes of cell-adhesion molecules.
Together, these findings provide a cell-type-resolved perspective on the molecular consequences of sleep deprivation in the hippocampus, revealing coordinated alteration across neuronal and glial populations that may corporately contribute to disrupted synaptic plasticity and memory processes. These results also suggest possible mechanisms through which chronic sleep disturbance may increase hippocampal vulnerability to neurodegenerative diseases.
Details
- Title: Subtitle
- The molecular impact of sleep deprivation on the hippocampus
- Creators
- Yutong Wang
- Contributors
- Edwin (Ted) Abel (Advisor)Mark S. Blumberg (Committee Member)Kamal Rahmouni (Committee Member)Jon M. Resch (Committee Member)Seth M. Tomchik (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Biomedical Science (Pharmacology)
- Date degree season
- Spring 2026
- DOI
- 10.25820/etd.008426
- Publisher
- University of Iowa
- Number of pages
- xv, 167 pages
- Copyright
- Copyright 2026 Yutong Wang
- Language
- English
- Date submitted
- 04/21/2026
- Description illustrations
- Illustrations, graphs, charts, tables
- Description bibliographic
- Includes bibliographical references (pages 146-167).
- Public Abstract (ETD)
Sleep plays important roles in maintaining brain functions, particularly processes involved in learning and memory. When sleep is insufficient, cognitive performance declines, and memory formation is impaired. The hippocampus, a brain region essential for memory, is especially sensitive to sleep loss. While previous studies have shown that sleep deprivation (SD) disrupts neuronal communication within the hippocampus, the molecular mechanism underlying these effects remain poorly understood. This thesis investigated how sleep deprivation alters molecular processes in the hippocampus across different cell types.
Neuronal activity was examined across hippocampal subregions following SD. The results showed that SD unevenly activates the hippocampus, with the CA1 subregion display the strongest activity induction. Using a genetic tagging approach, we identified a subset of CA1 neurons that are repeatedly activated during periods of SD. Translation profiling of these CA1 neurons revealed changes in protein synthesis, synaptic signaling, and metabolic pathways supporting neuronal plasticity. This work also examined non-neuronal cells that support brain functions. We found that transcription of genes involved in metabolic pathways in astrocytes and structural support in oligodendrocytes are altered by sleep loss.
Together, we demonstrated that sleep deprivation affects multiple interacting cell types within hippocampal circuits. Our data also provides new insights into how sleep loss disrupts brain function and may increase vulnerability to long-term neurological disorders.
- Academic Unit
- Neuroscience and Pharmacology
- Record Identifier
- 9985177175702771
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