Mapping functional and structural plasticity in the adult brain with novel volume imaging-based methods
Abstract/Contents
- Abstract
- The brain's capacity to reorganize is thought to diminish with age, yet ongoing anatomical plasticity in mature neural circuits is critical for functions like learning, memory, and the ability to recover from neurological injury and disease. Organismal experience can induce activity-dependent changes in axons, including outgrowth, branching, elongation, pruning, and elimination. Such changes have been well-studied during the "critical period" in early postnatal life. Changes of this nature have also been documented in the adult, but the logic, timing, and magnitude of axonal dynamics in this setting, and the molecular mechanisms that mediate them, remain poorly understood. This is due, in part, to the difficulty of developing robust systems to visualize and quantify concurrent structural, functional, and molecular changes across large volumes of the intact brain in 3D. In this dissertation I present several novel approaches to surmount this challenge, and I apply them to the study of activity-dependent axonal reorganization in the adult. First, I discuss critical improvements made to a whole-mount immunolabeling and tissue-clearing method called iDISCO which enable the automated registration of large cohorts of samples, imaged in volume by light sheet microscopy, to a standard reference brain atlas. Second, I describe the creation and optimization of a computational toolkit for the quantitative image analysis of immunolabeled structures in 3D. Third, I validate a data production pipeline combining these two innovations by mapping whole-brain perturbations in molecular markers of activity following acute and chronic sensory deprivation. Fourth, I employ novel viral and genetic tracing strategies to label, perturb, and quantify changes in activity-defined subcircuits following chronic sensory deprivation. Specifically, I demonstrate that different subcircuits in the mouse whisker barrel system follow different reorganizational rules, while the molecular mechanisms underlying their execution may be shared. This work advances our understanding of axonal plasticity in the adult brain and lays a methodologic foundation for future studies to systematically explore causal links between molecular, structural, and functional changes in intact neural circuits in both health and disease
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 | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Adams, Eliza Lynne |
|---|---|
| Degree supervisor | Luo, Liqun, 1966- |
| Degree supervisor | Tessier-Lavigne, Marc |
| Thesis advisor | Luo, Liqun, 1966- |
| Thesis advisor | Tessier-Lavigne, Marc |
| Thesis advisor | Huguenard, John |
| Thesis advisor | Monje-Deisseroth, Michelle |
| Thesis advisor | Shatz, Carla J |
| Degree committee member | Huguenard, John |
| Degree committee member | Monje-Deisseroth, Michelle |
| Degree committee member | Shatz, Carla J |
| Associated with | Stanford University, Neurosciences Program. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Eliza Lynne Adams |
|---|---|
| Note | Submitted to the Neurosciences Program |
| Thesis | Thesis Ph.D. Stanford University 2020 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Eliza Lynne Adams
- License
- This work is licensed under a Creative Commons Attribution Non Commercial No Derivatives 3.0 Unported license (CC BY-NC-ND).
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