Dissertation
Mapping activity-dependent gene expression in the brain
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2024
DOI: 10.25820/etd.007387
Abstract
Understanding brain function necessitates unraveling the molecular mechanisms governing memory consolidation and sleep deprivation. Leveraging spatial transcriptomics, we mapped gene expression changes across the hippocampus during memory consolidation in male mice. Each hippocampal subregion exhibited distinct yet overlapping transcriptomic signatures, with CA1 showing expression of genes related to transcriptional regulation and the DG exhibiting upregulation of genes associated with protein folding. Our approach also defined the transcriptomic signature of learning in less-explored CA1 subregions such as stratum radiatum and oriens. Furthermore, CA1 subregion-specific expression of a transcription factor subfamily played a critical role in long-term memory consolidation.
Memory consolidation is negatively impacted by sleep deprivation. Leveraging Translating ribosome affinity purification combined with unbiased RNA sequencing (TRAP-Seq), we investigated the effects of sleep deprivation on the translatome of the hippocampus, uncovering significant changes affecting the pool of actively translated mRNAs in male mice. Additionally, using spatial transcriptomics, we identified pronounced brain-wide gene expression changes in male mice, particularly in the hippocampus, neocortex, hypothalamus, and thalamus, suggesting altered gene expression patterns contribute to memory impairment.
The integrated spatial and single-cell transcriptomic profiling described in this thesis enhances our understanding of region and cell type-specific molecular signatures in memory, sleep, and neuronal activation within the brain, highlighting the interconnectedness of altered gene expression patterns during sleep deprivation with mechanisms associated with memory consolidation and neuronal activation.
Details
- Title: Subtitle
- Mapping activity-dependent gene expression in the brain
- Creators
- Yann Vanrobaeys
- Contributors
- Ted E Abel (Advisor)Thomas Nickl-Jockschat (Committee Member)Aislinn Williams (Committee Member)Marie E Gaine (Committee Member)Bin He (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Genetics
- Date degree season
- Spring 2024
- Publisher
- University of Iowa
- DOI
- 10.25820/etd.007387
- Number of pages
- xi, 164 pages
- Copyright
- Copyright 2024 Yann Vanrobaeys
- Grant note
- This work was supported by grants from the National Institute of Health R01 MH 087463 to T.A., The National Institute of Health K99/R00 AG068306 to S.C., and The University of Iowa Hawkeye Intellectual and Developmental Disabilities Research Center (HAWKIDDRC) P50 HD103556 to T.A. T.A. is also supported by the Roy J. Carver Charitable Trust. J.J.M. is supported by the Roy J. Carver associate professorship. (51)
- Language
- English
- Date submitted
- 04/22/2024
- Description illustrations
- illustrations, graphs
- Description bibliographic
- Includes bibliographical references (pages 139-164).
- Public Abstract (ETD)
- Exploring how our brains work involves understanding the very molecular processes behind memory, sleep, and brain activity that happen inside our cells. We used a technique called spatial transcriptomics to look at gene activity in different parts of the brain while mice were learning and forming memories. We found unique patterns of gene activity in each area, like increased activity in genes controlling how information is processed in the CA1 area and different genes being more active in the DG area, linked to folding proteins. We even explored less-known regions like stratum radiatum and oriens in CA1, uncovering the role of a specific gene family role in long-term memory. When it comes to sleep, we discovered that lack of sleep disturbs our genes. Using the same technique, we saw significant changes in gene activity throughout the brain, especially in areas tied to memory like the hippocampus. This suggests that the altered gene activity might be connected to memory troubles caused by lack of sleep. Additionally, using a technique called TRAP-seq, we studied how lack of sleep affects the activity of certain genes in the brain. We found that sleep deprivation caused notable changes in the types of genes being actively translated into proteins in male mice. Our combined spatial and single-cell approach helps us understand specific molecular patterns in memory, sleep, and brain activity. It shows how changes in gene activity during sleep deprivation are connected to the mechanisms behind both memory creation and brain activation.
- Academic Unit
- Interdisciplinary Graduate Program in Genetics
- Record Identifier
- 9984647555802771
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