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[IEEE 2018 EMF-Med 1st World Conference on Biomedical Applications of Electromagnetic Fields (EMF-Med) - Split, Croatia (2018.9.10-2018.9.13)] 2018 EMF-Med 1st World Conference on Biomedical Applications of Electromagnetic Fields (EMF-Med) - Comparison between Direct Electrical and Optogenetic Subthalamic Nucleus Stimulation
摘要： Subthalamic nucleus deep brain stimulation is a treatment for Parkinson’s disease. In this study, a computational model of a plateau-potential generating subthalamic nucleus neuron (Otsuka-model) and a four-state ChR2(H134R) model (Williams-model) are combined, in order to compare electrical and optogenetic neuromodulation capabilities. The impact of the stimulation modality (optogenetic or electric) on firing rates, strength-duration curves and action potential shape is investigated. First, in contrast to electrical stimulation, mean instantaneous firing rates saturate for optical stimulation at intensities higher than 0.1 W/cm2. Second, rheobase and chronaxie are 175% and 9.6% larger in optogenetic stimulation compared to electrical stimulation, respectively. Third, action potential shape is not significantly impacted by the neurostimulation modality.
关键词： Optogenetics,Channelrhodopsin-2 (H134R),subthalamic nucleus,Otsuka-model,computational modeling
更新于2025-09-10 09:29:36
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Engineering Improved Photoswitches for the Control of Nucleocytoplasmic Distribution
摘要： Optogenetic techniques use light-responsive proteins to study dynamic processes in living cells and organisms. These techniques typically rely on repurposed naturally occurring light-sensitive proteins to control sub-cellular localization and activity. We previously engineered two optogenetic systems, the Light Activated Nuclear Shuttle (LANS) and the Light-Inducible Nuclear eXporter (LINX), by embedding nuclear import or export sequence motifs into the C-terminal helix of the light-responsive LOV2 domain of Avena sativa phototropin 1, thus enabling light-dependent trafficking of a target protein into and out of the nucleus. While LANS and LINX are effective tools, we posited that mutations within the LOV2 hinge-loop, which connects the core PAS domain and the C-terminal helix, would further improve the functionality of these switches. Here, we identify hinge-loop mutations that favourably shift the dynamic range (the ratio of the on- to off-target subcellular accumulation) of the LANS and LINX photoswitches. We demonstrate the utility of these new optogenetic tools to control gene transcription and epigenetic modifications, thereby expanding the optogenetic ‘tool kit’ for the research community.
关键词： LANS,LINX,LOV2,dynamic range,Optogenetics,nucleocytoplasmic shuttle
更新于2025-09-10 09:29:36
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A Compact Wireless Power Transfer System at 915 MHz with Supercapacitor for Optogenetics Applications
摘要： To facilitate sophisticated optogenetics research with minimal disruption to animal’s behavior, a fully wireless optical stimulator module is desirable. This paper presents a compact wireless power transfer (WPT) system for optogenetics applications that is adapted to work in implanted condition with unstable and insufficient ambient RF energy field. The scope of this work is to design and implement a power transfer system architecture that is able to: 1) work over long distance, 2) achieve high power conversion efficiency and 3) provide stable output power for sufficient time duration. The designed WPT circuit operates at 915 MHz and achieves maximum power conversion efficiency of 50% at -15 dBm input power. With a compact circuitry design (12.20 × 13.22 mm), the obtained full power transmission efficiency was 0.329 % at 20 dBm (100 mW) transmission power. Ex-vivo experiments indicated that when the WPT system was located 10 cm from the source, it retrieved a maximum of 0.324 mW in free space, and 0.112 mW if inserted inside porcine cadaver meat with 4 cm of thickness. At a distance of 1 m from the source, the system retrieved 17 μW in free space, and 1 μW in porcine meat. Furthermore, to sufficiently drive the LED, an advanced supercapacitor was utilized as an energy storage element. When fully charged, the system can supply the LED over 75 seconds with a total power of 2.45 W. The developed WPT system can be a viable solution to be applied in optogenetic experiments on laboratory animals for preclinical studies.
关键词： Optogenetics,Bioimplantable,Wireless power transfer,Voltage multiplier,Supercapacitor
更新于2025-09-10 09:29:36
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An optimized and automated approach to quantifying channelrhodopsin photocurrent kinetics
摘要： Channelrhodopsins are light-activated ion channels that enable targetable activation or inhibition of excitable cells with light. Ion conductance can generally be described by a four step photocycle, which includes two open and two closed states. While a complete understanding of channelrhodopsin function cannot be understood in the absence of kinetic modeling, model fitting requires manual fitting, which is laborious and technically complicated for non-experts. To enhance analysis of photocurrent data, this manuscript describes a fitting program where electrophysiology data can be automatically and quantitatively analyzed. Significant improvement in this program when compare to our previous version includes 1) the ability to automatically find the experiment start time using the derivative of the current signal, 2) utilizing the Object Oriented Programing (OPP) paradigm which is significantly more reliable if the code is used by people with little to no programming experience and 3) the distribution of the code is simplified to sharing a single MATLAB file, including rigorous comments throughout. To demonstrate the utility of this program, we show automated fitting of photocurrents from two member proteins: channelrhodopsin-2 and a chimera between channelrhodopsin-1 and channelrhodopsin-2 (C1C2).
关键词： neuroscience,channelrhodopsin,optogenetics,kinetic modeling,electrophysiology
更新于2025-09-10 09:29:36
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Optogenetic dissection of Rac1 and Cdc42 gradient shaping
摘要： During cell migration, Rho GTPases spontaneously form spatial gradients that define the front and back of cells. At the front, active Cdc42 forms a steep gradient whereas active Rac1 forms a more extended pattern peaking a few microns away. What are the mechanisms shaping these gradients, and what is the functional role of the shape of these gradients? Here we report, using a combination of optogenetics and micropatterning, that Cdc42 and Rac1 gradients are set by spatial patterns of activators and deactivators and not directly by transport mechanisms. Cdc42 simply follows the distribution of Guanine nucleotide Exchange Factors, whereas Rac1 shaping requires the activity of a GTPase-Activating Protein, β2-chimaerin, which is sharply localized at the tip of the cell through feedbacks from Cdc42 and Rac1. Functionally, the spatial extent of Rho GTPases gradients governs cell migration, a sharp Cdc42 gradient maximizes directionality while an extended Rac1 gradient controls the speed.
关键词： Rac1,cell migration,micropatterning,optogenetics,GAPs,GEFs,Cdc42,β2-chimaerin,Rho GTPases
更新于2025-09-10 09:29:36
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Bringing Light to Transcription: The Optogenetics Repertoire
摘要： The ability to manipulate expression of exogenous genes in particular regions of living organisms has profoundly transformed the way we study biomolecular processes involved in both normal development and disease. Unfortunately, most of the classical inducible systems lack fine spatial and temporal accuracy, thereby limiting the study of molecular events that strongly depend on time, duration of activation, or cellular localization. By exploiting genetically engineered photo sensing proteins that respond to specific wavelengths, we can now provide acute control of numerous molecular activities with unprecedented precision. In this review, we present a comprehensive breakdown of all of the current optogenetic systems adapted to regulate gene expression in both unicellular and multicellular organisms. We focus on the advantages and disadvantages of these different tools and discuss current and future challenges in the successful translation to more complex organisms.
关键词： transcription,optogenetics,cryptochrome,phytochrome B,LOV,gene expression,UVR8,light
更新于2025-09-09 09:28:46
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Optogenetics in preclinical neuroscience and psychiatry research: recent insights and potential applications
摘要： There have been significant advances in the treatment of psychiatric disease in the last half century, but it is still unclear which neural circuits are ultimately responsible for specific disease states. Fortunately, technical limitations that have constrained this research have recently been mitigated by advances in research tools that facilitate circuit-based analyses. The most prominent of these tools is optogenetics, which refers to the use of genetically encoded, light-sensitive proteins that can be used to manipulate discrete neural circuits with temporal precision. Optogenetics has recently been used to examine the neural underpinnings of both psychiatric disease and symptom relief, and this research has rapidly identified novel therapeutic targets for what could be a new generation of rational drug development. As these and related methodologies for controlling neurons ultimately make their way into the clinic, circuit-based strategies for alleviating psychiatric symptoms could become a remarkably refined approach to disease treatment.
关键词： obsessive-compulsive disorder,optogenetics,addiction,anxiety,depression
更新于2025-09-09 09:28:46
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Wirelessly Operated, Implantable Optoelectronic Probes for Optogenetics in Freely Moving Animals
摘要： Recording and interrogating brain activities using optical methods have become emerging technologies in neuroscience. Traditional tools for optogenetic stimulation in the deep brain are mostly based on implantable fibers, imposing constraints on the animal movement. Recently developed microscale light-emitting diodes (micro-LEDs), which can be wirelessly operated, serve as injectable light sources that directly interact with neural systems. Here, we exploit a wirelessly controlled, implantable system for optogenetic studies in behaving animals. Thin-film indium gallium nitride (InGaN)-based blue micro-LEDs transferred onto flexible probes are injected into the animal brain and optically activate channelrhodopsin-2 expressing neurons. A customized circuit module with a battery is employed to modulate the micro-LED, which is remotely controlled at a distance up to 50 m via 2.4-GHz radio frequency communications. The systems are implemented on freely moving mice, and demonstrate optogenetic modulation of locomotive behaviors in vivo. Moreover, independent and synchronous control of multiple animals is accomplished with the communication unit in the design circuit. The proposed system provides the potential for advanced optical neural interfaces and offers solutions to study complicated animal behaviors in neuroscience research.
关键词： optogenetics,Implantable devices,micro-light-emitting diodes (LEDs),wireless operation
更新于2025-09-09 09:28:46
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Wiring the depressed brain: optogenetic and chemogenetic circuit interrogation in animal models of depression
摘要： The advent of optogenetics and chemogenetics has revolutionized the study of neural circuit mechanisms of behavioral dysregulation in psychiatric disease. These powerful technologies allow manipulation of specific neurons to determine causal relationships between neuronal activity and behavior. Optogenetic tools have been key to mapping the circuitry underlying depression-like behavior in animal models, clarifying the contribution of the ventral tegmental area, nucleus accumbens, medial prefrontal cortex, ventral hippocampus, and other limbic areas, to stress susceptibility. In comparison, chemogenetics have been relatively underutilized, despite offering unique advantages for probing long-term effects of manipulating neuronal activity. The ongoing development of optogenetic tools to probe in vivo function of ever-more specific circuits, combined with greater integration of chemogenetic tools and recent advances in vivo imaging techniques will continue to advance our understanding of the circuit mechanisms of depression.
关键词： chemogenetics,neural circuits,optogenetics,animal models,depression
更新于2025-09-04 15:30:14
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Developing an Outcome Measure With High Luminance for Optogenetics Treatment of Severe Retinal Degenerations and for Gene Therapy of Cone Diseases
摘要： PURPOSE. To present stimuli with varied sizes, colors, and patterns over a large range of luminance. METHODS. The ?lter bar used in scotopic MP1 was replaced with a custom slide-in tray that introduces light from an external projector driven by an additional computer. MP1 software was modi?ed to provide retinal tracking information to the computer driving the projector. Retinal tracking performance was evaluated by imaging the system input and the output simultaneously with a high-speed video system. Spatial resolution was measured with achromatic and chromatic grating/background combinations over scotopic and photopic ranges. RESULTS. The range of retinal illuminance achievable by the modi?cation was up to 6.8 log photopic Trolands (phot-Td); however, in the current work, only a lower range over (cid:2)4 to t3 log phot-Td was tested in human subjects. Optical magni?cation was optimized for low-vision testing with gratings from 4.5 to 0.2 cyc/deg. In normal subjects, spatial resolution driven by rods, short wavelength-sensitive (S-) cones, and long/middle wavelength-sensitive (L/M-) cones was obtained by the choice of adapting conditions and wavelengths of grating and background. Data from a patient with blue cone monochromacy was used to con?rm mediation. CONCLUSIONS. The modi?ed MP1 can be developed into an outcome measure for treatments in patients with severe retinal degeneration, very low vision, and abnormal eye movements such as those for whom treatment with optogenetics is planned, as well as for patients with cone disorders such as blue cone monochromacy for whom treatment with gene therapy is planned to improve L/M-cone function above a normal complement of rod and S-cone function.
关键词： retinal degeneration,outcome measures,low vision,optogenetics,channelrhodopsin
更新于2025-09-04 15:30:14