Neuronal MHCI function in developmental critical periods and neurological disorders
Abstract/Contents
- Abstract
- Neuronal circuits dynamically strengthen or weaken through experience-regulated processes during developmental windows of synaptic plasticity. In this thesis, I test the hypothesis that two specific Major Histocompatibility Complex Class I (MHCI) genes, H2-Kb and H2-Db, restrict cortical plasticity during both developmental and adult neurological disorders. Mice lacking H2-Kb and H2-Db (KbDb KOs) have enhanced ocular dominance plasticity and excessive cortical connectivity. In a model of the autism-spectrum disorder Rett Syndrome, developmental ocular dominance plasticity is impaired, and H2-Db expression is elevated. In an adult model of stroke called middle cerebral artery occlusion, H2-Kb and H2-Db expression is elevated in the damaged hemisphere, and expression and downstream signaling of the MHCI receptor PirB are increased. KbDb and PirB KO mice have smaller infarcted regions and better motor recovery, and PirB KOs have enhanced circuit remapping in the corticospinal tract, which could contribute to improved motor function. Together, results suggest that H2-Kb and H2-Db function to constrain plasticity in juvenile and adult cerebral cortex. Moreover, an over-expression of these two MHCIs may contribute to Rett Syndrome and impede recovery following stroke. H2-Kb and H2-Db and their receptor PirB therefore may represent important therapeutic targets for disorders typified by abnormal synaptic plasticity.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2014 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Adelson, Jaimie |
|---|---|
| Associated with | Stanford University, Neurosciences Program. |
| Primary advisor | Shatz, Carla J |
| Thesis advisor | Shatz, Carla J |
| Thesis advisor | Hestrin, Shaul |
| Thesis advisor | McConnell, Susan K |
| Thesis advisor | Raymond, Jennifer L |
| Advisor | Hestrin, Shaul |
| Advisor | McConnell, Susan K |
| Advisor | Raymond, Jennifer L |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Jaimie Adelson. |
|---|---|
| Note | Submitted to the Program in Neurosciences. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Jaimie Dolgin Adelson
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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