Mechanisms of deep brain stimulation revealed by optogenetic deconstruction of diseased brain circuitry
Abstract/Contents
- Abstract
- Deep brain stimulation (DBS) is a powerful therapeutic option for intractable movement and affective disorders (Parkinson's disease or PD, tremor, dystonia, Tourette syndrome, chronic pain, obsessive compulsive disorder, depression, bipolar). The benefits of DBS are immediate and dramatic, manifested as instantaneous improvements in motor function in the case of PD patients. However, due to the nonspecificity of electrical stimulation, DBS has variable efficacy and can lead to serious side effects. The mechanisms behind the effects of DBS are still highly controversial and there is tremendous interest from both neuroscience and clinical communities to understand and improve DBS. We have developed a novel technology based on two microbial opsins, Channelrhodopsin (ChR2) and Halorhodopsin (NpHR), that allows to directly and specifically control the activity of distinct cell-types with high temporal precision in well defined brain regions, therefore allowing us to overcome the lack of specificity of electrical DBS. This study provides the first investigation of the role of specific cell types in ameliorating PD symptoms addressed by effective DBS treatment. The focus of the thesis was twofold: (1) to develop and optimize optogenetic technologies (molecular and hardware) for safe and effective use in behaving mammals; and (2) to employ the above developed optogenetic toolkit to deconstructing diseased brain circuitry, with focus on Parkinson's disease. The framework and technological toolbox presented here can be employed across many brain circuits to selectively control individual components and therefore systematically deconstruct intact and disordered brain processes.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Gradinaru, Viviana |
|---|---|
| Associated with | Stanford University, Department of Neurosciences. |
| Primary advisor | Deisseroth, Karl |
| Thesis advisor | Deisseroth, Karl |
| Thesis advisor | Bronte-Stewart, Helen |
| Thesis advisor | Buckmaster, Paul S |
| Thesis advisor | Shatz, Carla J |
| Advisor | Bronte-Stewart, Helen |
| Advisor | Buckmaster, Paul S |
| Advisor | Shatz, Carla J |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Viviana Gradinaru. |
|---|---|
| Note | Submitted to the Department of Neurosciences. |
| Thesis | Ph. D. Stanford University 2010 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Viviana Gradinaru
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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