Featured
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| Open AccessT-DOpE probes reveal sensitivity of hippocampal oscillations to cannabinoids in behaving mice
Neural activity is regulated by synapse-neuromodulator interactions, necessitating optoelectro-pharmacological investigations. Here, authors implement their multi-modal probe to show focal infusion of synthetic cannabinoid disrupts CA1 oscillations.
- Jongwoon Kim
- , Hengji Huang
- & Xiaoting Jia
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Article
| Open AccessProgrammable RNA base editing with photoactivatable CRISPR-Cas13
Cas13 systems suffer from a lack of spatiotemporal control. Here the authors report paCas13, a light-inducible Cas13 system created by fusing Magnet with fragment pairs; they also report padCas13, a light-inducible base-editing system by fusing ADAR2 to catalytically inactive paCas13 fragments.
- Jeonghye Yu
- , Jongpil Shin
- & Won Do Heo
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Article
| Open AccessHijacking of internal calcium dynamics by intracellularly residing viral rhodopsins
Rhodopsins are ubiquitous light-driven membrane proteins that have diverse functions in nature, and value as optogenetics tools. Here the authors characterise type 1 viral channelrhodopsins, showing that they regulate intracellular calcium and can be used for the photocontrol of muscle contraction in vivo.
- Ana-Sofia Eria-Oliveira
- , Mathilde Folacci
- & Michel Vivaudou
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Article
| Open AccessOptogenetic spatial patterning of cooperation in yeast populations
Microbial communities are the siege of complex metabolic interactions including cooperation and competition. Here, the authors report the utilization of optogenetics and spatial light-patterning to activate the expression of the invertase SUC2 at selected locations and selectively switch cooperation and competition roles of the yeast cells.
- Matthias Le Bec
- , Sylvain Pouzet
- & Pascal Hersen
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Article
| Open AccessOptogenetic control of YAP reveals a dynamic communication code for stem cell fate and proliferation
The transcriptional regulator YAP controls cellular decisions such as proliferation, differentiation, and pluripotency. Here, the authors show a concentration-dependent and temporal communication code for YAP that enables cells to choose between these programs.
- Kirstin Meyer
- , Nicholas C. Lammers
- & Orion D. Weiner
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Article
| Open AccessReversible photoregulation of cell-cell adhesions with opto-E-cadherin
Tools for high spatiotemporal control of cell-cell adhesions are lacking. Here, authors propose an optogenetic tool, opto-E-cadherin, that allows reversible control of E-cadherin-mediated cell-cell adhesions with blue light.
- Brice Nzigou Mombo
- , Brent M. Bijonowski
- & Seraphine V. Wegner
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Article
| Open AccessAll-optical spatiotemporal mapping of ROS dynamics across mitochondrial microdomains in situ
How ROS diffuse and are cleared between mitochondrial compartments governs oxidative stress and cell signaling. Here, authors map the kinetics of ROS dynamics using optogenetics and discover acute ROS transiently elongates mitochondria.
- Shon A. Koren
- , Nada Ahmed Selim
- & Andrew P. Wojtovich
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Article
| Open AccessOptimized virtual optical waveguides enhance light throughput in scattering media
Virtual optical waveguide can be potentially utilised in variety of applications that require in situ light steering yet the efficacy is still unclear. Here, the authors show that ultrasonically-sculpted virtual gradient-index waveguides are effective in guiding and confining light inside tissue and other scattering media, and significantly outperform external lenses at this task.
- Adithya Pediredla
- , Matteo Giuseppe Scopelliti
- & Ioannis Gkioulekas
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Article
| Open AccessOptogenetic engineering of STING signaling allows remote immunomodulation to enhance cancer immunotherapy
Optogenetics makes use of light-sensitive proteins to control biological processes using light. Here, the authors present an optogenetic system that regulates the cGAS/STING pathway remotely and demonstrate its efficacy in murine tumour models.
- Yaling Dou
- , Rui Chen
- & Yun Huang
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Article
| Open AccessMultidimensional characterization of inducible promoters and a highly light-sensitive LOV-transcription factor
The ability to independently control the expression of different genes is important for quantitative biology. Here, the authors report kinetic parameters, noise scaling, impact on growth, and the fundamental leakiness of a wide range of inducible transcriptional systems, including a new, highly light sensitive LOV-transcription factor.
- Vojislav Gligorovski
- , Ahmad Sadeghi
- & Sahand Jamal Rahi
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Article
| Open AccessAn optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells
Different activation patterns of Akt kinase direct downstream signaling outcomes. Here, the authors run phosphoproteomics on optogenetically-activated Akt1 to characterize the phosphorylation circuits induced by different intensities, durations, and patterns of stimulation.
- Wenping Zhou
- , Wenxue Li
- & Yansheng Liu
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Article
| Open AccessLight-switchable transcription factors obtained by direct screening in mammalian cells
Light-switchable variants are only available for a limited subset of proteins and pathways. Here the authors adapt strategies for protein domain insertion and mammalian-cell expression to generate and screen a library of potential optogenetic tools directly in mammalian cells.
- Liyuan Zhu
- , Harold M. McNamara
- & Jared E. Toettcher
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Article
| Open AccessMaximizing protein production by keeping cells at optimal secretory stress levels using real-time control approaches
Optimisation of production of recombinant proteins is pharmaceutically important. Here, the authors identify a state of secretion burnout for cells and report a strategy in which induction is dynamically adjusted based on the current cell stress to avoid the appearance of burnt-out cells.
- Sebastián Sosa-Carrillo
- , Henri Galez
- & Gregory Batt
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Article
| Open AccessA visual opsin from jellyfish enables precise temporal control of G protein signalling
Jellyfish see light in a similar way that vertebrates smell odours. Here, Michiel van Wyk and Sonja Kleinlogel show how jellyfish has adapted this slow signal detection pathway to support sophisticated vision, and use a similar method to restore vision in blind mice.
- Michiel van Wyk
- & Sonja Kleinlogel
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Article
| Open AccessFunctional MRI reveals brain-wide actions of thalamically-initiated oscillatory activities on associative memory consolidation
Thalamic spindle activities may support memory consolidation. Here the authors show that optogenetically-evoked somatosensory thalamic spindle-like activity enhances memory performance in male rats.
- Xunda Wang
- , Alex T. L. Leong
- & Ed X. Wu
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Article
| Open AccessControlling protein stability with SULI, a highly sensitive tag for stabilization upon light induction
Tools for the spatiotemporal control of protein abundance are valuable in studying diverse complex biological processes. Here, authors engineered a protein tag which is stabilized upon light induction but which quickly degrades the protein of interest in the dark, demonstrating control of protein stability in yeast and zebrafish.
- Miaowei Mao
- , Yajie Qian
- & Yi Yang
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Article
| Open AccessAll-optical closed-loop voltage clamp for precise control of muscles and neurons in live animals
Optogenetic actuation regimes are often static, which allows perturbation, but not true control of neuronal activity. Here, the authors describe an all-optical method for bidirectional steering of membrane potential, in closed loop, in C. elegans muscles and neurons, and rat hippocampal slice culture. The ‘optogenetic voltage clamp’ uses two microbial rhodopsin actuators and the rhodopsin voltage indicator QuasAr.
- Amelie C. F. Bergs
- , Jana F. Liewald
- & Alexander Gottschalk
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Article
| Open AccessOptical control of PIEZO1 channels
PIEZO proteins are large, mechanically-activated trimeric ion channels. Here the authors report a light-gated mouse PIEZO1 channel, mOP1, whereby an azobenzene-based photoswitch covalently localised at the extracellular apex of a transmembrane helix, rapidly triggers channel gating on light irradiation.
- Francisco Andrés Peralta
- , Mélaine Balcon
- & Thomas Grutter
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Article
| Open AccessLight-driven biological actuators to probe the rheology of 3D microtissues
The mechanical properties of biological tissues are key to their integrity and function. Here, the authors engineer 3D microtissues from optogenetically modified fibroblasts and use light to quantify tissue elasticity and strain propagation using their own constituent cells as internal actuators.
- Adrien Méry
- , Artur Ruppel
- & Thomas Boudou
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| Open AccessCalcium-permeable channelrhodopsins for the photocontrol of calcium signalling
To date, no Ca2 + -selective channelrhodopsins have been characterized. In this study, Fernandez Lahore et al. report two calcium-permeable channelrhodopsins (CapChR1 and 2) for the photocontrol of calcium signalling in excitable tissue.
- Rodrigo G. Fernandez Lahore
- , Niccolò P. Pampaloni
- & Peter Hegemann
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| Open AccessRapid and reversible optogenetic silencing of synaptic transmission by clustering of synaptic vesicles
Existing optogenetic silencing methods affect membrane potential, biochemistry or protein integrity. Here, the authors demonstrate an approach for silencing synaptic transmission that combines fast activation and reversibility, by using nondisruptive, reversible, light-evoked clustering of synaptic vesicles, which they validate in Caenorhabditis elegans, zebrafish, and murine cell culture.
- Dennis Vettkötter
- , Martin Schneider
- & Alexander Gottschalk
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Article
| Open AccessDeep brain stimulation creates informational lesion through membrane depolarization in mouse hippocampus
The neurophysiological mechanisms of deep brain stimulation remain poorly understood. Through fluorescence voltage imaging of individual hippocampal neurons in awake mice, the authors show that deep brain stimulation causes membrane depolarization that impairs a neuron’s ability to respond to intrinsic network activity patterns and optogenetic somatic depolarization, thereby creating an informational lesion.
- Eric Lowet
- , Krishnakanth Kondabolu
- & Xue Han
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Article
| Open AccessActivated astrocytes attenuate neocortical seizures in rodent models through driving Na+-K+-ATPase
Neocortical epilepsy is resistant to current treatments. Zhao et al. report that optogenetic stimulation of astrocytes effectively attenuates seizures via driving Na+-K+-ATPase, indicating a potential treatment strategy for intractable epilepsy.
- Junli Zhao
- , Jinyi Sun
- & Yi Wang
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Article
| Open AccessA doxycycline- and light-inducible Cre recombinase mouse model for optogenetic genome editing
Achieving spatial control of gene expression is important. Here the authors report an optimised photoactivatable Cre recombinase system, doxycycline- and light-inducible Cre recombinase (DiLiCre), and generate a DiLiCre mouse line which they use for mutagenesis in vivo and positional cell-tracing.
- Miguel Vizoso
- , Colin E. J. Pritchard
- & Jacco van Rheenen
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Article
| Open AccessOptogenetic-controlled immunotherapeutic designer cells for post-surgical cancer immunotherapy
The induction of long-term systemic immunosurveillance can protect against post-surgery tumor recurrence. Here the authors describe the design of optogenetic-controlled cytokine secreting (IFN-β, TNF-α, and IL-12) engineered mesenchymal stem cells loaded into a hydrogel scaffold, eliciting long-term immune memory and preventing post-operative recurrence in preclinical cancer models.
- Yuanhuan Yu
- , Xin Wu
- & Haifeng Ye
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Article
| Open AccessWireless multi-lateral optofluidic microsystems for real-time programmable optogenetics and photopharmacology
Wireless delivery of both light and pharmacological agents is important for optogenetic and other mechanistic experiments in the brain. Here the authors present a wireless real-time programmable optofluidic platform that enables optogenetics and photopharmacology experiments that require real-time precise control of light and drug delivery.
- Yixin Wu
- , Mingzheng Wu
- & John A. Rogers
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Article
| Open AccessOptogenetic control of apical constriction induces synthetic morphogenesis in mammalian tissues
Apical constriction is a force-generating process required during embryonic development; there is a lack of tools to manipulate 3D shapes of mammalian tissues. Here the authors report the optogenetic method, OptoShroom3, to achieve fast spatiotemporal control of apical constriction in mammalian epithelia.
- Guillermo Martínez-Ara
- , Núria Taberner
- & Miki Ebisuya
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Article
| Open AccessDynamic cybergenetic control of bacterial co-culture composition via optogenetic feedback
Communities of microbes play important roles in natural environments and hold great potential for deploying division-of-labor strategies in synthetic biology and bioproduction. Here, in a community of two competing E. coli strains, the authors show that the relative abundances of the strains can be stabilized and steered dynamically with remarkable precision by coupling the cells to an automated computer-controlled feedback-loop.
- Joaquín Gutiérrez Mena
- , Sant Kumar
- & Mustafa Khammash
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Article
| Open AccessDefunctionalizing intracellular organelles such as mitochondria and peroxisomes with engineered phospholipase A/acyltransferases
Approaches for manipulating individual organelles are important for learning more about their functions. Here the authors report a tool utilising phospholipase A/acyltransferases (PLAATs) for rapid defunctionalisation of organelles through remodelling of the membrane phospholipids.
- Satoshi Watanabe
- , Yuta Nihongaki
- & Takanari Inoue
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Article
| Open AccessLight-activated mitochondrial fission through optogenetic control of mitochondria-lysosome contacts
Existing methods can lack spatiotemporal accuracy to manipulate dynamic mitochondrial behaviour in live cells. Here the authors report an optogenetic method to control mitochondria-lysosome contacts and induce mitochondrial fission; they use photoactivatable dimerizers including CRY2/CIB and SspB/iLID.
- Kangqiang Qiu
- , Weiwei Zou
- & Jiajie Diao
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Article
| Open AccessEfficient spatially targeted gene editing using a near-infrared activatable protein-conjugated nanoparticle for brain applications
Spatial control of gene expression allows precise control over biological processes. Here, the authors develop an efficient light-responsive formulation based on upconversion nanoparticles, and demonstrate on-demand genetic manipulation in deep brain tissue.
- Catarina Rebelo
- , Tiago Reis
- & Lino Ferreira
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Article
| Open AccessControlling synthetic membraneless organelles by a red-light-dependent singlet oxygen-generating protein
Membraneless organelles play vital cellular roles, and control over their formation and state could have varied applications. Here, the authors develop photoresponsive synthetic condensates whose activity can be controlled through the use of light to trigger liquid-to-solid phase transition.
- Manjia Li
- , Byung Min Park
- & Fei Sun
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Article
| Open AccessOptogenetic manipulation and photoacoustic imaging using a near-infrared transgenic mouse model
Optogenetic tools can be used as in vivo imaging probes. Here the authors generate a loxP-BphP1 transgenic mouse to enable Cre-dependent temporal and spatial targeting of BphP1 expression in vivo; they show photoacoustic tomography of BphP1 expression in developing embryos and regenerating livers.
- Ludmila A. Kasatkina
- , Chenshuo Ma
- & Vladislav V. Verkhusha
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Article
| Open AccessA reversible mitochondrial complex I thiol switch mediates hypoxic avoidance behavior in C. elegans
Mitochondria regulate diverse cellular signalling processes in addition to producing energy. Here, the authors show a mitochondrial redox switch that, when activated, helps nematode worms sense conditions of low environmental oxygen.
- John O. Onukwufor
- , M. Arsalan Farooqi
- & Andrew P. Wojtovich
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Article
| Open AccessA hierarchy of biomolecular proportional-integral-derivative feedback controllers for robust perfect adaptation and dynamic performance
The design of feedback biomolecular controllers is essential to synthetically regulate biological processes in a robust and timely fashion. Here the authors introduce a wide array of biomolecular Proportional-Integral-Derivative (PID) controllers that are capable of enhancing stability and dynamic performance, and also reducing stochastic noise.
- Maurice Filo
- , Sant Kumar
- & Mustafa Khammash
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Article
| Open AccessSelective optogenetic control of Gq signaling using human Neuropsin
Gq proteins are one of four major classes of G proteins; optogenetic receptors for selective and repetitive activation of Gq proteins with fast kinetics are lacking. Here the authors report UV light-dependent Gq signalling using human Neuropsin (hOPN5) and demonstrate its potential as an optogenetic tool.
- Ahmed Wagdi
- , Daniela Malan
- & Tobias Bruegmann
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Article
| Open AccessColocalized, bidirectional optogenetic modulations in freely behaving mice with a wireless dual-color optoelectronic probe
Simultaneous neural activation and inhibition in the same brain region of animals is highly desirable. Here the authors report a wireless, dual-colour optogenetic probe with the co-expression of two spectrally distinct opsins to allow for bidirectional neuronal activity manipulation in a rodent model.
- Lizhu Li
- , Lihui Lu
- & Xing Sheng
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Article
| Open AccessAn optogenetic approach for regulating human parathyroid hormone secretion
Parathyroid hormone (PTH) plays a role in maintaining calcium and phosphorus homeostasis, and in secondary hyperparathyroidism excess PTH secretion contributes to bone loss. Here the authors report an optogenetic approach to inhibit PTH secretion in human hyperplastic parathyroid cells, and prevented hyperplastic parathyroid tissue-induced bone loss in mice.
- Yunhui Liu
- , Lu Zhang
- & Fan Yang
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Article
| Open AccessGasdermin D pores are dynamically regulated by local phosphoinositide circuitry
During pyroptosis, gasdermin D (GSDMD) forms plasma membrane pores that initiate cell lysis. Here, the authors develop optogenetically activatable human GSDMD to assess GSDMD pore behavior and show that they are dynamic and can close, which can be a pyroptosis regulatory mechanism.
- Ana Beatriz Santa Cruz Garcia
- , Kevin P. Schnur
- & Gary C. H. Mo
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Article
| Open AccessOptogenetic relaxation of actomyosin contractility uncovers mechanistic roles of cortical tension during cytokinesis
The subcellular dynamics of actomyosin contractility is currently hard to study. Here the authors report OptoMYPT, an optogenetic method to induce relaxation of actomyosin contractility by allowing light-dependent recruitment of endogenous protein phosphatase 1c (PP1c) to the plasma membrane.
- Kei Yamamoto
- , Haruko Miura
- & Kazuhiro Aoki
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Article
| Open AccessSelf-assembled multifunctional neural probes for precise integration of optogenetics and electrophysiology
The authors present a viral vector-delivery optrode system to integrate optogenetics and electrophysiology. The flexible microelectrode filaments and fiber optics self-assemble in a nanoliter-scale, viral vector-delivery polymer carrier for localized delivery and expression of opsin genes at microelectrode-tissue interfaces.
- Liang Zou
- , Huihui Tian
- & Ying Fang
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Article
| Open AccessA light tunable differentiation system for the creation and control of consortia in yeast
Artificial microbial consortia use division-of-labour to optimize production. Here the authors develop an optogenetic differentiation system in yeast to generate consortia from a single strain with tunable composition.
- Chetan Aditya
- , François Bertaux
- & Jakob Ruess
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Article
| Open AccessEnabling comprehensive optogenetic studies of mouse hearts by simultaneous opto-electrical panoramic mapping and stimulation
Current cardiac mapping systems provide either electrical or optical readouts. Here the authors report a panoramic opto-electrical measurement and stimulation (POEMS) system which embraces the entire ventricular surface of mouse hearts, allowing flexible combinations of optical and electrical recording and stimulation modalities.
- Michael Rieger
- , Christian Dellenbach
- & Stephan Rohr
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Article
| Open AccessNear-infrared manipulation of multiple neuronal populations via trichromatic upconversion
Conventional upconversion nanoparticles (UCNPs) cannot activate multiple neuron populations independently using optogenetics. Here the authors report trichromatic UCNPs with excitation-specific luminescence to allow activation of three distinct neuronal populations in the brain of awake mice.
- Xuan Liu
- , Heming Chen
- & Fan Zhang
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Article
| Open AccessRapid prototyping and design of cybergenetic single-cell controllers
Practical implementation of genetic circuits is difficult due to low predictability and time-intensive troubleshooting. Here the authors present Cyberloop, which interfaces a computer with single cells to enable cell-in-the-loop testing and optimization of circuit designs before they are built.
- Sant Kumar
- , Marc Rullan
- & Mustafa Khammash
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Article
| Open AccessAn active tethering mechanism controls the fate of vesicles
Molecular tethers physically bridge transport vesicles to their target membranes as a prerequisite step for fusion. Here the authors control vesicle tethering using optogenetic approaches to study the interplay between vesicle tethering and fusion.
- Seong J. An
- , Felix Rivera-Molina
- & Derek Toomre
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Article
| Open AccessMEG source imaging detects optogenetically-induced activity in cortical and subcortical networks
Identifying causal interactions between brain regions is important to understand its computations. Here the authors present optoMEG, a platform for combining optogenetic techniques with high-resolution magnetic source imaging in nonhuman primates to map network activation.
- Gregory E. Alberto
- , Jennifer R. Stapleton-Kotloski
- & Dwayne W. Godwin
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Article
| Open AccessBiPOLES is an optogenetic tool developed for bidirectional dual-color control of neurons
Currently, bidirectional control of activity in the same neurons in the same experiment is difficult. Here the authors report a Bidirectional Pair of Opsins for Light-induced Excitation and Silencing, BiPOLES, which they use in a range of organisms including worms, fruit flies, mice and ferrets.
- Johannes Vierock
- , Silvia Rodriguez-Rozada
- & J. Simon Wiegert
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Article
| Open AccessRemote control of neural function by X-ray-induced scintillation
Scintillators emit visible luminescence when irradiated with X-rays and may enable remote optogenetic control of neurons deep in the brain. The authors inject an inorganic scintillator to activate and inhibit midbrain dopamine neurons in freely moving mice by X-ray irradiation to modulate place preference behavior.
- Takanori Matsubara
- , Takayuki Yanagida
- & Takayuki Yamashita