Adaptive myelination in the mammalian brain

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Abstract/Contents

Abstract
Myelin sheaths, specialized segments of oligodendrocyte plasma membranes in the central nervous system, facilitate fast, saltatory conduction of action potentials down axons. Myelination of the central nervous system requires the generation of functionally mature oligodendrocytes from oligodendrocyte precursor cells. Changes to the fine structure of myelin in a neural circuit are expected to affect conduction velocity of action potentials. Recent evidence from humans and animal models suggests that myelination may be sensitive to experiences during development and adulthood, and that varying levels of neuronal activity may underlie these experience-dependent changes in myelin and myelin-forming cells, perhaps selectively instructing myelination of an active neural circuit. In this thesis, I present work using optogenetic stimulation of premotor cortex in awake, behaving mice to demonstrate that neuronal activity elicits a mitogenic response of neural and oligodendrocyte precursor cells, promotes oligodendrogenesis and increases myelination within the deep layers of the premotor cortex and subcortical white matter. Neuronal activity-regulated oligodendrogenesis and myelination is associated with improved motor function of the corresponding limb. Oligodendrogenesis and myelination appear necessary for the observed functional improvement, as epigenetic blockade of oligodendrocyte differentiation and myelin changes prevents the activity-regulated behavioral improvement. A deeper understanding of adaptive myelination may provide insights into diseases involving damage and dysregulation of myelin and myelin-forming cells.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2015
Issuance monographic
Language English

Creators/Contributors

Associated with Purger, David Arnold
Associated with Stanford University, Department of Stem Cell Biology and Regenerative Medicine Interdisciplinary.
Primary advisor Monje-Deisseroth, Michelle
Thesis advisor Monje-Deisseroth, Michelle
Thesis advisor Palmer, Theo
Thesis advisor Wyss-Coray, Anton
Advisor Palmer, Theo
Advisor Wyss-Coray, Anton

Subjects

Genre Theses

Bibliographic information

Statement of responsibility David Arnold Purger.
Note Submitted to the Department of Stem Cell Biology and Regenerative Medicine Interdisciplinary.
Thesis Thesis (Ph.D.)--Stanford University, 2015.
Location electronic resource

Access conditions

Copyright
© 2015 by David Purger
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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