Optogenetic tool development and application to dissecting dopaminergic circuitry in social behavior
Abstract/Contents
- Abstract
- Social interaction is an essential and highly integrative behavioral task that is impaired in major psychiatric disorders such as autism, schizophrenia, social anxiety disorder, and depression. Current treatments for many of these disorders are based on pharmacological approaches that have been used for decades even though their mechanisms of action are poorly understood and carry many side effects. In particular, treatment of the asocial symptoms of these disorders has remained elusive due to a generally poor understanding of the neural circuitry underlying normal social behavior. In order to move toward a deeper circuit-level understanding of these complex neural processes, our lab has pioneered the use of two light-activated microbial opsins, Channelrhodopsin-2 (ChR2) and Halorhodopsin (NpHR), to achieve precise bidirectional optogenetic control of specific cell types in behaving animals. However, it has become clear that the complexity of the circuitry involved in psychiatric behaviors will require new classes of optogenetic tools to modulate cells in a more refined manner based on characteristics such as projection profile, receptor expression, and endogenous firing patterns. The purpose of this study was thus two-fold: 1) to develop novel optogenetic tools for more physiologically relevant stimulation of different cell types on different timescales, and 2) to apply these tools to define in socializing animals the real-time causal role not only of a specific brain region and cell type, but also of distinct subpopulations defined by projections to different downstream brain regions and distinct downstream cell types. The engineered opsins we develop here will be generalizable to dissect other neural circuits in health and disease, enabling new domains of optogenetic investigation that have thus far been inaccessible, and enhancing the precision of optical neural control in a broad variety of settings.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2012 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Gunaydin, Lisa Aila |
|---|---|
| Associated with | Stanford University, Department of Neurosciences. |
| Primary advisor | Deisseroth, Karl |
| Thesis advisor | Deisseroth, Karl |
| Thesis advisor | Knutson, Brian |
| Thesis advisor | Malenka, Robert C |
| Thesis advisor | Shatz, Carla J |
| Advisor | Knutson, Brian |
| Advisor | Malenka, Robert C |
| Advisor | Shatz, Carla J |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Lisa Gunaydin. |
|---|---|
| Note | Submitted to the Department of Neurosciences. |
| Thesis | Ph.D. Stanford University 2012 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2012 by Lisa Aila Gunaydin
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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