The Experts below are selected from a list of 28311 Experts worldwide ranked by ideXlab platform
Karl Deisseroth - One of the best experts on this subject based on the ideXlab platform.
-
A Proof-of-Principle of Nanoscale Optogenetics
2018Co-Authors: Markus A. Stahlberg, Karl Deisseroth, Edward S Boyden, Charu Ramakrishnan, Katrin I. Willig, Camin DeanAbstract:Optogenetics has revolutionized the study of circuit function in the brain, by allowing activation of specific ensembles of neurons by light. However, this technique has not yet been exploited extensively at the subcellular level. Here we propose a novel focal stimulation approach using STED/RESOLFT-like illumination, whereby switchable light-gated channels are focally activated by a laser beam of one wavelength and deactivated by an overlapping donut-shaped beam of a different wavelength, confining activation to a center focal region. We demonstrate the utility of current optogenetic tools to achieve highly focal depolarization using this method and further examine a proof-of-principle of nanoscale optogenetic activation using an initial macroscale approach. When employed at the nanoscale, this approach will allow unprecedented optogenetic control of nanodomains within cells.
-
integration of Optogenetics with complementary methodologies in systems neuroscience
Nature Reviews Neuroscience, 2017Co-Authors: Christina K Kim, Karl Deisseroth, Avishek AdhikariAbstract:Modern Optogenetics can be tuned to evoke activity that corresponds to naturally occurring local or global activity in timing, magnitude or individual-cell patterning. This outcome has been facilitated not only by the development of core features of Optogenetics over the past 10 years (microbial-opsin variants, opsin-targeting strategies and light-targeting devices) but also by the recent integration of Optogenetics with complementary technologies, spanning electrophysiology, activity imaging and anatomical methods for structural and molecular analysis. This integrated approach now supports optogenetic identification of the native, necessary and sufficient causal underpinnings of physiology and behaviour on acute or chronic timescales and across cellular, circuit-level or brain-wide spatial scales.
-
beyond the brain optogenetic control in the spinal cord and peripheral nervous system
Science Translational Medicine, 2016Co-Authors: Kate L Montgomery, Karl Deisseroth, Shrivats Mohan Iyer, Amelia J Christensen, Scott L DelpAbstract:Optogenetics offers promise for dissecting the complex neural circuits of the spinal cord and peripheral nervous system and has therapeutic potential for addressing unmet clinical needs. Much progress has been made to enable optogenetic control in normal and disease states, both in proof-of-concept and mechanistic studies in rodent models. In this Review, we discuss challenges in using Optogenetics to study the mammalian spinal cord and peripheral nervous system, synthesize common features that unite the work done thus far, and describe a route forward for the successful application of Optogenetics to translational research beyond the brain.
-
Optogenetics: Opsins and Optical Interfaces in Neuroscience
Cold Spring Harbor protocols, 2014Co-Authors: Antoine Adamantidis, Feng Zhang, Luis De Lecea, Karl DeisserothAbstract:Optogenetics is defined as the integration of optics and genetics to control well-defined events within specified cells of living tissue. In this introduction, we focus on the basic techniques necessary for employing microbial opsins as optogenetic tools in mammalian brains. We provide a guide for the fundamentals of optogenetic application-selecting an opsin, implementing expression of opsins based on the neuroscientific experimental requirements, and adapting the corresponding optical hardware for delivery of light into mammalian brains.
-
Optogenetics and psychiatry applications challenges and opportunities
Biological Psychiatry, 2012Co-Authors: Karl DeisserothAbstract:Achievingcircuit-levelinsightintothefundamentalnatureof psychiatric symptoms has long proven elusive. Technological limitations have traditionally prevented cell type-targeted and temporally precise interventions into intact mammalian neural circuitry to elicit or ameliorate expression of disease symptom-related phenotypes. However, recent years have seen a growing wave of applications of Optogenetics to questions in neuropsychiatric disease, with the deployment of millisecond-precision optical excitation or inhibition of specific circuit elements within behavingmammals.Indeed,optogenetictechnologynowexistsin a special relationship with psychiatry because one of the unique andmostversatilefeaturesofOptogenetics(modulationofdefined neural projections) is well aligned with what may be a core feature of psychiatric disease (altered function along pathways of neural communication). In this special issue, we collect perspectives from leading researchers at the convergence of psychiatry and Optogenetics, highlighting the fundamental questions that have been addressed and many of the opportunities that remain. The convergence of Optogenetics (1‐3) and psychiatry has occurredrapidlyoverthelastfewyears,withenoughcomplexitythat a review and update of the core technology is useful in this venue before review of the psychiatry applications. Therefore, this special issue opens with a detailed summary of optogenetic technology itself from an Optogenetics pioneer. Mei and Zhang (4) lead with a detailed and concise introduction to the diversity of microbial opsin-based optogenetic tools, the basic principles of operation, and the suite of enabling technologies that have been developed. Most important among the associated enabling technologies (especially from the perspective of psychiatry) was the fiber optic neural interface, which overcame the depth limitation caused by light scattering and allowed access to (and optogenetic control of) any brain region even in freely moving mammals. This device debuted in 2007 (5) and was first applied (also in 2007) to address questions relevant to narcolepsy and sleep-wake transitions (6). Specificactivitypatternswereplayedintotargetedhypocretinneurons in the lateral hypothalamus in freely moving mice; certain
Wim Vanduffel - One of the best experts on this subject based on the ideXlab platform.
-
Optogenetics in primates: a shining future?
Trends in genetics : TIG, 2013Co-Authors: Annelies Gerits, Wim VanduffelAbstract:To understand the functional role of specific neurons in micro- and macro-brain circuitry, health, and disease, it is critical to control their activity precisely. This ambitious goal was first achieved by Optogenetics, allowing researchers to increase or decrease neural activity artificially with high temporal and spatial precision. In contrast to the revolution Optogenetics engendered in invertebrate and rodent research, only a few studies have reported optogenetic-induced neuronal and behavioral effects in primates. Such studies are nonetheless critical before Optogenetics can be applied in a clinical setting. Here, we review the state-of-the-art tools for performing Optogenetics in mammals, emphasizing recent neuronal and behavioral results obtained in nonhuman primates.
-
optogenetically induced behavioral and functional network changes in primates
Current Biology, 2012Co-Authors: Annelies Gerits, Reza Farivar, Bruce R Rosen, Lawrence L Wald, Edward S Boyden, Wim VanduffelAbstract:Summary Optogenetics is currently the state-of-the-art method for causal-oriented brain research. Despite an increasingly large number of invertebrate and rodent studies showing profound electrophysiological and behavioral effects induced by Optogenetics [1, 2], only two primate studies have reported modulation of local single-cell activity but with no behavioral effects [3, 4]. Here, we show that optogenetic stimulation of cortical neurons within rhesus monkey arcuate sulcus, during the execution of a visually guided saccade task, evoked significant and reproducible changes in saccade latencies as a function of target position. Moreover, using concurrent optogenetic stimulation and opto-fMRI [5, 6]), we observed optogenetically induced changes in fMRI activity in specific functional cortical networks throughout the monkey brain. This is critical information for the advancement of optogenetic primate research models and for initiating the development of optogenetically based cell-specific therapies with which to treat neurological diseases in humans.
Xiaogang Liu - One of the best experts on this subject based on the ideXlab platform.
-
Upconversion Nanoparticle-Mediated Optogenetics.
Advances in experimental medicine and biology, 2021Co-Authors: Angelo H. All, Xiaogang LiuAbstract:Upconversion nanoparticle-mediated Optogenetics enables remote delivery of upconverted visible light from a near-infrared light source to targeted neurons or areas, with the precision of a pulse of laser light in vivo for effective deep-tissue neuromodulation. Compared to conventional optogenetic tools, upconversion nanoparticle-based optogenetic techniques are less invasive and cause reduced inflammation with minimal levels of tissue damage. In addition to the optical stimulation, this design offers simultaneously temperature recording in proximity to the stimulated area. This chapter strives to provide life science researchers with an introduction to upconversion Optogenetics, starting from the fundamental concept of photon upconversion and nanoparticle fabrication to the current state-of-the-art of surface engineering and device integration for minimally invasive neuromodulation.
Kay M. Tye - One of the best experts on this subject based on the ideXlab platform.
-
Optogenetic investigation of neural circuits underlying brain disease in animal models
Nature Reviews Neuroscience, 2012Co-Authors: Kay M. Tye, Karl DeisserothAbstract:Key Points'Optogenetic' approaches (the use of light-sensitive genetically encodable tools to manipulate cellular activity) in neuroscience have matured beyond the proof-of-principle phase and have grown into a widely used set of techniques for dissecting the circuits underlying behaviour. Recent technological advances include the integration of Optogenetics with established techniques in electrophysiology and pharmacology, as well as the expansion of the optogenetic toolbox to include new opsin variants and new transgenic rodent lines. Optogenetic approaches provide new advantages such as precise cellular targeting and greater temporal control, but also bring new limitations that are important to consider, such as heating artefacts and problems with light delivery and overexpression toxicity. Optogenetic approaches have led to the dissection of microcircuits in the amygdala underlying fear and anxiety and to the discovery of unexpectedly broad temporal regimes in which the hippocampus is involved in recalling remote memories. The use of Optogenetics to target a specific projection or specific cell type in transgenic Cre recombinase rodents has advanced our understanding of the circuits underlying reward-related learning relevant to addiction. Manipulating parvalbumin neurons, rhythmic oscillations and the balance of excitation and inhibition in neocortex using optogenetic tools has advanced our understanding of schizophrenia- and autism-related phenomena. The use of optogenetic methods has advanced our understanding of neurological disorders and treatments, clarifying our understanding of deep brain stimulation and striatal circuits in the context of Parkinson's disease.AbstractOptogenetic tools have provided a new way to establish causal relationships between brain activity and behaviour in health and disease. Although no animal model captures human disease precisely, behaviours that recapitulate disease symptoms may be elicited and modulated by optogenetic methods, including behaviours that are relevant to anxiety, fear, depression, addiction, autism and parkinsonism. The rapid proliferation of optogenetic reagents together with the swift advancement of strategies for implementation has created new opportunities for causal and precise dissection of the circuits underlying brain diseases in animal models.Optogenetics enables the precise and targeted manipulation of the activity of specific neurons and is a powerful tool for the dissection of neural circuits. Tye and Deisseroth describe the latest refinements in optogenetic technology and show how this approach is being used to investigate the circuits involved in psychiatric and neurological disorders.
-
amygdala circuitry mediating reversible and bidirectional control of anxiety
Nature, 2011Co-Authors: Kay M. Tye, Lief E Fenno, Charu Ramakrishnan, Rohit Prakash, Sungyon Kim, Logan Grosenick, Hosniya Zarabi, Kimberly R Thompson, Viviana Gradinaru, Karl DeisserothAbstract:Anxiety--a sustained state of heightened apprehension in the absence of immediate threat--becomes severely debilitating in disease states. Anxiety disorders represent the most common of psychiatric diseases (28% lifetime prevalence) and contribute to the aetiology of major depression and substance abuse. Although it has been proposed that the amygdala, a brain region important for emotional processing, has a role in anxiety, the neural mechanisms that control anxiety remain unclear. Here we explore the neural circuits underlying anxiety-related behaviours by using Optogenetics with two-photon microscopy, anxiety assays in freely moving mice, and electrophysiology. With the capability of Optogenetics to control not only cell types but also specific connections between cells, we observed that temporally precise optogenetic stimulation of basolateral amygdala (BLA) terminals in the central nucleus of the amygdala (CeA)--achieved by viral transduction of the BLA with a codon-optimized channelrhodopsin followed by restricted illumination in the downstream CeA--exerted an acute, reversible anxiolytic effect. Conversely, selective optogenetic inhibition of the same projection with a third-generation halorhodopsin (eNpHR3.0) increased anxiety-related behaviours. Importantly, these effects were not observed with direct optogenetic control of BLA somata, possibly owing to recruitment of antagonistic downstream structures. Together, these results implicate specific BLA-CeA projections as critical circuit elements for acute anxiety control in the mammalian brain, and demonstrate the importance of optogenetically targeting defined projections, beyond simply targeting cell types, in the study of circuit function relevant to neuropsychiatric disease.
Annelies Gerits - One of the best experts on this subject based on the ideXlab platform.
-
Optogenetics in primates: a shining future?
Trends in genetics : TIG, 2013Co-Authors: Annelies Gerits, Wim VanduffelAbstract:To understand the functional role of specific neurons in micro- and macro-brain circuitry, health, and disease, it is critical to control their activity precisely. This ambitious goal was first achieved by Optogenetics, allowing researchers to increase or decrease neural activity artificially with high temporal and spatial precision. In contrast to the revolution Optogenetics engendered in invertebrate and rodent research, only a few studies have reported optogenetic-induced neuronal and behavioral effects in primates. Such studies are nonetheless critical before Optogenetics can be applied in a clinical setting. Here, we review the state-of-the-art tools for performing Optogenetics in mammals, emphasizing recent neuronal and behavioral results obtained in nonhuman primates.
-
optogenetically induced behavioral and functional network changes in primates
Current Biology, 2012Co-Authors: Annelies Gerits, Reza Farivar, Bruce R Rosen, Lawrence L Wald, Edward S Boyden, Wim VanduffelAbstract:Summary Optogenetics is currently the state-of-the-art method for causal-oriented brain research. Despite an increasingly large number of invertebrate and rodent studies showing profound electrophysiological and behavioral effects induced by Optogenetics [1, 2], only two primate studies have reported modulation of local single-cell activity but with no behavioral effects [3, 4]. Here, we show that optogenetic stimulation of cortical neurons within rhesus monkey arcuate sulcus, during the execution of a visually guided saccade task, evoked significant and reproducible changes in saccade latencies as a function of target position. Moreover, using concurrent optogenetic stimulation and opto-fMRI [5, 6]), we observed optogenetically induced changes in fMRI activity in specific functional cortical networks throughout the monkey brain. This is critical information for the advancement of optogenetic primate research models and for initiating the development of optogenetically based cell-specific therapies with which to treat neurological diseases in humans.