Article

Optogenetics in Neural Systems

Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Neuron (Impact Factor: 15.05). 07/2011; 71(1):9-34. DOI: 10.1016/j.neuron.2011.06.004
Source: PubMed

ABSTRACT

Both observational and perturbational technologies are essential for advancing the understanding of brain function and dysfunction. But while observational techniques have greatly advanced in the last century, techniques for perturbation that are matched to the speed and heterogeneity of neural systems have lagged behind. The technology of optogenetics represents a step toward addressing this disparity. Reliable and targetable single-component tools (which encompass both light sensation and effector function within a single protein) have enabled versatile new classes of investigation in the study of neural systems. Here we provide a primer on the application of optogenetics in neuroscience, focusing on the single-component tools and highlighting important problems, challenges, and technical considerations.

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    • "Yet, the spatiotemporal precision of ACC neuronal activity in pain remains enigmatic and the function of different ACC neuronal subtypes is controversial. Optogenetic tools are increasingly being used to identify the neural circuits underlying various types of behaviors or to reveal the functions of specific subtypes of cells [27, 28] . Several cre line mice are available for the selective manipulation of specific cell types [29, 30]. "

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    • "This method is routinely used to target either neurons or excitatory neurons using the human synapsin (hSyn) or CaMKIIα promoters, and can be particularly effective when used for projection targeting. Using this approach, a fiber optic is implanted over a downstream brain region rather than over the infected cell bodies, which allows for pathway-specific modulation of neural activity (Yizhar et al., 2011a; Tye and Deisseroth, 2012). Some viral vectors have been developed to target specific genetically defined cell classes, but the majority of cell types require more genetic material to confer specificity than allowed by this approach. "
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    ABSTRACT: This review, one of a series of articles, tries to make sense of optogenetics, a recently developed technology that can be used to control the activity of genetically defined neurons with light. Cells are first genetically engineered to express a light-sensitive opsin, which is typically an ion channel, pump, or G protein-coupled receptor. When engineered cells are then illuminated with light of the correct frequency, opsin-bound retinal undergoes a conformational change that leads to channel opening or pump activation, cell depolarization or hyperpolarization, and neural activation or silencing. Since the advent of optogenetics many different opsin variants have been discovered or engineered, and it is now possible to stimulate or inhibit neuronal activity or intracellular signaling pathways on fast or slow timescales with a variety of different wavelengths of light. Optogenetics has been successfully employed to enhance our understanding of the neural circuit dysfunction underlying mood disorders, addiction, and Parkinson's disease, and has enabled us to achieve a better understanding of the neural circuits mediating normal behavior. It has revolutionized the field of neuroscience, and has enabled a new generation of experiments that probe the causal roles of specific neural circuit components. © The Author 2015. Published by Oxford University Press on behalf of CINP.
    Full-text · Article · Jul 2015 · The International Journal of Neuropsychopharmacology
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    • "absorption coefficient of brain tissue. Thus, previous studies of light spread (Yizhar et al., 2011; Aravanis et al., 2007; Bernstein et al., 2008) would not be sensitive to the choice of model parameters, while heat predictions would be highly affected. To test the accuracy of the model with the two parameter sets, we measured heat changes in brain tissue in vivo under continuous light stimulation. "
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    ABSTRACT: Despite the increasing use of optogenetics in vivo, the effects of direct light exposure to brain tissue are understudied. Of particular concern is the potential for heat induced by prolonged optical stimulation. We demonstrate that high-intensity light, delivered through an optical fiber, is capable of elevating firing rate locally, even in the absence of opsin expression. Predicting the severity and spatial extent of any temperature increase during optogenetic stimulation is therefore of considerable importance. Here, we describe a realistic model that simulates light and heat propagation during optogenetic experiments. We validated the model by comparing predicted and measured temperature changes in vivo. We further demonstrate the utility of this model by comparing predictions for various wavelengths of light and fiber sizes, as well as testing methods for reducing heat effects on neural targets in vivo. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
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