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


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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Available from: Ofer Yizhar,
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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.
    The International Journal of Neuropsychopharmacology 07/2015; DOI:10.1093/ijnp/pyv079 · 4.01 Impact Factor
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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.
    Cell Reports 07/2015; 12(3). DOI:10.1016/j.celrep.2015.06.036 · 8.36 Impact Factor
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    • "Light output was measured with an optical power meter and adjusted to *7 mW of 561 nm light. Based on in vivo measurements, of light output in mammalian brain tissue, these parameters would be expected to provide sufficient light to at least 0.4 mm 3 of tissue (Yizhar et al. 2011). Light was applied continuously for the first 15 min of the reinstatement session. "
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    ABSTRACT: Animal models of relapse reveal that the motivation to seek drug is regulated by enduring morphological and physiological changes in the nucleus accumbens, as well as transient synaptic potentiation in the accumbens core (NAcore) that parallels drug-seeking behavior. The current study sought to examine the link between the behavioral and synaptic consequences of cue-induced cocaine seeking by optically silencing glutamatergic afferents to the NAcore from the prelimbic cortex (PL). Adeno-associated virus coding for the inhibitory opsin archaerhodopsin was microinjected into PL, and optical fibers were targeted to NAcore. Animals were trained to self-administer cocaine followed by extinction training, and then underwent cue-induced reinstatement in the presence or absence of 15 min of optically induced inhibition of PL fibers in NAcore. Inhibiting the PL-to-NAcore projection blocked reinstated behavior and was paralleled by decreased dendritic spine head diameter and AMPA/NMDA ratio relative to sham-laser control rats. Interestingly, while spine density was elevated after extinction training, no further effects were observed by cued reinstatement or optical inhibition. These findings validate the critical role for PL afferents to the NAcore in simultaneously regulating both reinstated behavior and the associated transient synaptic potentiation.
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