Next-Generation Optical Technologies for Illuminating Genetically Targeted Brain Circuits

Duke University, Durham, North Carolina, United States
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 11/2006; 26(41):10380-6. DOI: 10.1523/JNEUROSCI.3863-06.2006
Source: PubMed


Emerging technologies from optics, genetics, and bioengineering are being combined for studies of intact neural circuits. The rapid progression of such interdisciplinary "optogenetic" approaches has expanded capabilities for optical imaging and genetic targeting of specific cell types. Here we explore key recent advances that unite optical and genetic approaches, focusing on promising techniques that either allow novel studies of neural dynamics and behavior or provide fresh perspectives on classic model systems.

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    • "To enable temporally precise control of specific cell types within behaving animals, fast ''optogenetic'' (Deisseroth et al., 2006) technologies have been developed involving singlecomponent light-responsive proteins that transduce brief pulses of light into well-defined action potential trains and effector functions in vivo (Boyden et al., 2005; Zhang et al., 2007a, 2007b). Through the use of optogenetics, precisely timed gainof-function or loss-of-function of specified events can be achieved in targeted cells of freely moving mammals and other animals (Adamantidis et al., 2007). "
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    DESCRIPTION: Molecular and Cellular Approaches for Diversifying and Extending Optogenetics (Viviana Gradinaru,Feng Zhang) university of california , los anjeles and caltech
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    • " presumably because these channels require PI ( 4 , 5 ) P 2 to remain open , and PI3K activity lowers PI ( 4 , 5 ) P 2 levels . Light can thus be used to modulate the activity of specific channels native to animals , as opposed to light - gated microbial opsin ion channels or pumps , the concept that originally gave rise to the term optogenetics ( Deisseroth et al . , 2006 ) . A potential advantage of modulating native - type channels is preservation of the channel responses to endogenous neuronal activity and localization to specific subcellular compartments . This could represent an alternative approach to lumitoxins to modulate the activity of specific channels that are native to animals ."
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    ABSTRACT: In the nervous system, protein activities are highly regulated in space and time. This regulation allows for fine modulation of neuronal structure and function during development and adaptive responses. For example, neurite extension and synaptogenesis both involve localized and transient activation of cytoskeletal and signaling proteins, allowing changes in microarchitecture to occur rapidly and in a localized manner. To investigate the role of specific protein regulation events in these processes, methods to optically control the activity of specific proteins have been developed. In this review, we focus on how photosensory domains enable optical control over protein activity and have been used in neuroscience applications. These tools have demonstrated versatility in controlling various proteins and thereby cellular functions, and possess enormous potential for future applications in nervous systems. Just as optogenetic control of neuronal firing using opsins has changed how we investigate the function of cellular circuits in vivo, optical control may yet yield another revolution in how we study the circuitry of intracellular signaling in the brain.
    Frontiers in Molecular Neuroscience 08/2015; 8:37. DOI:10.3389/fnmol.2015.00037 · 4.08 Impact Factor
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    • "As is well known in the many experimental tests of natural or sexual selection it is often difficult to attain a definitive test but this does not mean that one should not try. With the advent of a new generation of brain manipulation methods such as optogenetic approaches (Deisseroth et al., 2006) or CRISPR (Wiedenheft et al., 2012) relatively specific brain manipulations are becoming more feasible. However, the diversity in the mechanisms mediating the origin of sex differences as reviewed in this paper is an important reminder that sex differences in the brain and behavior can arise through a surprising variety of mechanisms that are consistent with many different adaptive and non-adaptive scenarios. "
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    ABSTRACT: Many sex differences in brain and behavior related to reproduction are thought to have evolved based on sexual selection involving direct competition for mates during male-male competition and female choice. Therefore, certain aspects of brain circuitry can be viewed as secondary sexual characteristics. The study of proximate causes reveals that sex differences in the brain of mammals and birds reflect organizational and activational effects of sex steroids as articulated by Young and collaborators. However, sex differences in brain and behavior have been identified in the cognitive domain with no obvious link to reproduction. Recent views of sexual selection advocate for a broader view of how intra-sexual selection might occur including such examples as competition within female populations for resources that facilitate access to mates rather than mating competition per se. Sex differences can also come about for other reasons than sexual selection and recent work on neuroendocrine mechanisms has identified a plethora of ways that the brain can develop in a sex specific manner. Identifying the brain as sexually selected requires careful hypothesis testing so that one can link a sex-biased aspect of a neural trait to a behavior that provides an advantage in a competitive mating situation.
    Neuroscience & Biobehavioral Reviews 10/2014; 46. DOI:10.1016/j.neubiorev.2014.08.009 · 8.80 Impact Factor
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