How does oligodendrocyte calcium signaling regulate central nervous system myelination?
Abstract/Contents
- Abstract
- In this dissertation, I examine the role of oligodendrocyte calcium signaling in regulating myelination and oligodendrocyte cell biology, both in the context of development and during learning and plasticity. Myelin is essential for rapid nerve signaling is increasingly found to play important roles in learning and in diverse diseases of the CNS. Morphological parameters of myelin such as sheath length and thickness are regulated by neuronal activity and are likely critical for fine-tuning conduction velocity, but the mechanisms controlling sheath morphology are poorly understood. Local calcium signaling has been observed in nascent myelin sheaths and can be modulated by neuronal activity. However, the role of calcium signaling in sheath formation and remodeling is unknown. In this dissertation, I have developed a suite of pharmacological and genetically-encoded tools to attenuate calcium during active myelination in the developing mouse CNS. I found that genetic calcium attenuation did not grossly abrogate myelin formation. Instead, calcium attenuation caused myelin defects: shorter myelin sheaths with abnormal morphology. Mechanistically, I found that dysregulation of myelin morphology was accompanied by reductions in actin filaments, and that an intact actin cytoskeleton was necessary and sufficient to achieve accurate myelin morphology. To follow up on this, I have begun to investigate the role of oligodendrocyte calcium signaling in regulating SNARE-mediated exocytosis. Second, I have found, excitingly, that oligodendrocyte calcium signaling is required for the acquisition of a dexterous forelimb reach task, suggesting that calcium signaling in oligodendrocytes may act as a cell biological bridge between neuronal activity and experience-dependent myelination. Together, my work reveals novel cellular mechanisms required for accurate CNS myelin formation and provides mechanistic insight into how oligodendrocytes may respond to neuronal activity to precisely sculpt myelin sheaths throughout the nervous system.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Iyer, Manasi |
|---|---|
| Degree supervisor | Zuchero, J |
| Thesis advisor | Zuchero, J |
| Thesis advisor | Cyert, Martha |
| Thesis advisor | Monje-Deisseroth, Michelle |
| Thesis advisor | Shatz, Carla |
| Degree committee member | Cyert, Martha |
| Degree committee member | Monje-Deisseroth, Michelle |
| Degree committee member | Shatz, Carla |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Neurosciences Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Manasi Iyer. |
|---|---|
| Note | Submitted to the Neurosciences Program. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/xb587pb7940 |
Access conditions
- Copyright
- © 2023 by Manasi Iyer
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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