Development of optogenetics for motor systems neuroscience in non-human primates
Abstract/Contents
- Abstract
- Voluntary movement is such an integral part of common tasks that the loss of this ability is detrimental to quality of life. Effective functional restoration for patients with a limited ability to move requires deep understanding of movement control. However, despite decades of motor system research, the mechanism by which motor cortex controls movement is still unclear. Although technological advances such as electrical microstimulation have been used to investigate this mechanism, its limitations in simultaneous recording and perturbation have prevented us from obtaining more informative measurements. To address this challenge, a multidisciplinary approach was taken to further examine the underlying mechanism of motor control. Specifically, we used optogenetics along with the analytical framework of dynamical systems theory to probe the dynamics of motor preparation. Three major results are presented in this work. Firstly, we characterized and assessed the functionality of optogenetics electrophysiologically and histologically in non-human primates. Although optogenetics has been used extensively in rodents, it is still in a developmental state in primates. Hence, the efficiency of virus transfection, the reliability of neural responses to optical stimulation, the pattern of opsin expression and the safety to animals were investigated to minimize any potential risk and to aid future experimental designs. We also discovered that, in contrast to electrical microstimulation, optical stimulation in cortical motor and premotor areas did not evoke overt skeletal movements. Secondly, we continued the characterization process by injecting a red-shifted opsin, C1V1(TT), in dorsal premotor cortex (PMd) and optically perturbed the neural activity while the animals were actively engaged in an instructed-delay reach task. We found that the optical perturbation in PMd resulted in increased reach reaction times. Moreover, using the dynamical systems perspective, we discovered that, post-perturbation, the neural state did not return to its pre-perturbed state. Instead, it proceeded directly to re-join the normal neural trajectory path to execute the movement. We also observed that optical stimulation did not obliterate task-related activity in light-responsive neurons. In fact, the relationship between task-related and optically-evoked activities appeared to be linearly additive. Lastly, we developed a decoding algorithm to extract kinematics information from optogenetically-perturbed data. We trained a Kalman filter based on a mixture of perturbed and unperturbed data, and found that it provided us with an effective decoder. This decoding performance was achieved despite the fact that the decoder made no attempt to detect whether or not the neural activity was perturbed.
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 | Goo, Werapong |
|---|---|
| Associated with | Stanford University, Department of Bioengineering. |
| Primary advisor | Shenoy, Krishna V. (Krishna Vaughn) |
| Thesis advisor | Shenoy, Krishna V. (Krishna Vaughn) |
| Thesis advisor | Deisseroth, Karl |
| Thesis advisor | Delp, Scott |
| Advisor | Deisseroth, Karl |
| Advisor | Delp, Scott |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Werapong Goo. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Werapong Goo
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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