Development of novel optogenetic and molecular tools and their application to understanding the neurological basis of behavior
- Successful interaction between an animal and its environment requires the execution of meaningful action in response to external cues and, in most situations, interpretation and integration of sensory inputs in the context of experience. Neurological and psychiatric diseases encompass dysfunction at any point in this pipeline. Neuroscientists seek to understand how the brain is able to complete these tasks in the healthy individual as well as the changes that underlie impairment in disease. The heterogeneous and highly interconnected structure of the brain creates unique hurdles to scientists that ask these questions. In many cases, traditional tools of the trade, namely, electrical and pharmacologic interventions, both fall short when used to derive definitive and generalizable conclusions. To facilitate neuroscience research, our laboratory has discovered, optimized, and diversified an array of single component, optically activated ion channels and pumps for neuronal control. These may be selectively introduced to neurons based on genetic or topological parameters, thereby selecting needles in the haystack of cells within the brain, and are modulated by light on the order of milliseconds, a scale relevant to neuronal activity. The purpose of the studies described here was two-fold: 1) to expand the toolbox through opsin engineering, light delivery methods, and molecular targeting strategies and 2) to apply these to understand the neurological basis of some psychiatric diseases. The use of these tools in understanding anxiety and social behavior circuitry is described briefly, while the application of two novel opsin variants to understanding the role of increased amounts of excitation relative to inhibition within the prefrontal cortex is detailed. The tools described here are designed for and validated within the brain, but may be applied within most biological systems. As experimental approaches expand, so do the range of questions available to science. Answers to these will lead to advances in understanding, managing, and curing injury and disease.
|Type of resource
|electronic; electronic resource; remote
|1 online resource.
|Fenno, Lief Ericsson
|Stanford University, Department of Neurosciences.
|Luo, Liqun, 1966-
|Luo, Liqun, 1966-
|Statement of responsibility
|Lief Ericsson Fenno.
|Submitted to the Department of Neurosciences.
|Thesis (Ph.D.)--Stanford University, 2014.
- © 2014 by Lief Ericsson Fenno
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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