Modeling the Spatiotemporal Dynamics of Light and Heat Propagation for In Vivo Optogenetics.
Ontology highlight
ABSTRACT:
SUBMITTER: Stujenske JM
PROVIDER: S-EPMC4512881 | biostudies-literature | 2015 Jul
REPOSITORIES: biostudies-literature
Publications
Modeling the Spatiotemporal Dynamics of Light and Heat Propagation for In Vivo Optogenetics.
Stujenske Joseph M JM Spellman Timothy T Gordon Joshua A JA
Cell reports 20150709 3
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 consi ...[more]
Similar Datasets
Project description:Spatiotemporal information about light pulse propagation obtained with femtosecond temporal resolution plays an important role in understanding transient phenomena and light-matter interactions. Although ultrafast optical imaging techniques have been developed, it is still difficult to capture light pulse propagation spatiotemporally. Furthermore, imaging through a three-dimensional (3-D) scattering medium is a longstanding challenge due to the optical scattering caused by the interaction between light pulse and a 3-D scattering medium. Here, we propose a technique for ultrafast optical imaging of light pulses propagating inside a 3D scattering medium. We record an image of the light pulse propagation using the ultrashort light pulse even when the interaction between light pulse and a 3-D scattering medium causes the optical scattering. We demonstrated our proposed technique by recording converging, refracted, and diffracted propagating light for 59 ps with femtosecond temporal resolution.
| S-EPMC8576009 | biostudies-literature
Project description:The purpose of this study is to model the dynamics of lobular Ca(2+) wave propagation induced by an extracellular stimulus, and to analyze the effect of spatially systematic variations in cell-intrinsic signaling parameters on sinusoidal Ca(2+) response.We developed a computational model of lobular scale Ca(2+) signaling that accounts for receptor- mediated initiation of cell-intrinsic Ca(2+) signal in hepatocytes and its propagation to neighboring hepatocytes through gap junction-mediated molecular exchange.Analysis of the simulations showed that a pericentral-to-periportal spatial gradient in hormone sensitivity and/or rates of IP3 synthesis underlies the Ca(2+) wave propagation. We simulated specific cases corresponding to localized disruptions in the graded pattern of these parameters along a hepatic sinusoid. Simulations incorporating locally altered parameters exhibited Ca(2+) waves that do not propagate throughout the hepatic plate. Increased gap junction coupling restored normal Ca(2+) wave propagation when hepatocytes with low Ca(2+) signaling ability were localized in the midlobular or the pericentral region.Multiple spatial patterns in intracellular signaling parameters can lead to Ca(2+) wave propagation that is consistent with the experimentally observed spatial patterns of Ca(2+) dynamics. Based on simulations and analysis, we predict that increased gap junction-mediated intercellular coupling can induce robust Ca(2+) signals in otherwise poorly responsive hepatocytes, at least partly restoring the sinusoidally oriented Ca (2+) waves.Our bottom-up model of agonist-evoked spatial Ca(2+) patterns can be integrated with detailed descriptions of liver histology to study Ca(2+) regulation at the tissue level.
| S-EPMC5035187 | biostudies-literature
Project description:Some of the most clinically consequential aspects of focal epilepsy, e.g. loss of consciousness, arise from the generalization or propagation of seizures through local and large-scale neocortical networks. Yet, the dynamics of such neocortical propagation remain poorly understood. Here, we studied the microdynamics of focal seizure propagation in neocortical patches (4×4 mm) recorded via high-density microelectrode arrays (MEAs) implanted in people with pharmacologically resistant epilepsy. Our main findings are threefold: (1) a newly developed stage segmentation method, applied to local field potentials (LFPs) and multiunit activity (MUA), revealed a succession of discrete seizure stages, each lasting several seconds. These different stages showed characteristic evolutions in overall activity and spatial patterns, which were relatively consistent across seizures within each of the 5 patients studied. Interestingly, segmented seizure stages based on LFPs or MUA showed a dissociation of their spatiotemporal dynamics, likely reflecting different contributions of non-local synaptic inputs and local network activity. (2) As previously reported, some of the seizures showed a peak in MUA that happened several seconds after local seizure onset and slowly propagated across the MEA. However, other seizures had a more complex structure characterized by, for example, several MUA peaks, more consistent with the succession of discrete stages than the slow propagation of a simple wavefront of increased MUA. In both cases, nevertheless, seizures characterized by spike-wave discharges (SWDs, ~2-3 Hz) eventually evolved into patterns of phase-locked MUA and LFPs. (3) Individual SWDs or gamma oscillation cycles (25-60 Hz), characteristic of two different types of recorded seizures, tended to propagate with varying degrees of directionality, directions of propagation and speeds, depending on the identified seizure stage. However, no clear relationship was observed between the MUA peak onset time (in seizures where such peak onset occurred) and changes in MUA or LFP propagation patterns. Overall, our findings indicate that the recruitment of neocortical territories into ictal activity undergoes complex spatiotemporal dynamics evolving in slow discrete states, which are consistent across seizures within each patient. Furthermore, ictal states at finer spatiotemporal scales (individual SWDs or gamma oscillations) are organized by slower time scale network dynamics evolving through these discrete stages.
| S-EPMC4618174 | biostudies-literature
Project description:Propagation of non-linear waves is key to the functioning of diverse biological systems. Such waves can organize into spirals, rotating around a core, whose properties determine the overall wave dynamics. Theoretically, manipulation of a spiral wave core should lead to full spatiotemporal control over its dynamics. However, this theory lacks supportive evidence (even at a conceptual level), making it thus a long-standing hypothesis. Here, we propose a new phenomenological concept that involves artificially dragging spiral waves by their cores, to prove the aforementioned hypothesis in silico, with subsequent in vitro validation in optogenetically modified monolayers of rat atrial cardiomyocytes. We thereby connect previously established, but unrelated concepts of spiral wave attraction, anchoring and unpinning to demonstrate that core manipulation, through controlled displacement of heterogeneities in excitable media, allows forced movement of spiral waves along pre-defined trajectories. Consequently, we impose real-time spatiotemporal control over spiral wave dynamics in a biological system.
| S-EPMC6195347 | biostudies-literature
Project description:Calcium is a ubiquitous second messenger that mediates vital physiological responses such as fertilization, secretion, gene expression, or apoptosis. Given this variety of processes mediated by Ca(2+), these signals are highly organized both in time and space to ensure reliability and specificity. This review deals with the spatiotemporal organization of the Ca(2+) signaling pathway in electrically nonexcitable cells in which InsP(3) receptors are by far the most important Ca(2+) channels. We focus on the aspects of this highly regulated dynamical system for which an interplay between experiments and modeling is particularly fruitful. In particular, the importance of the relative densities of the different InsP(3) receptor subtypes will be discussed on the basis of a modeling approach linking the steady-state behaviors of these channels in electrophysiological experiments with their behavior in a cellular environment. Also, the interplay between InsP(3) metabolism and Ca(2+) oscillations will be considered. Finally, we discuss the relationships between stochastic openings of the Ca(2+) releasing channels at the microscopic level and the coordinated, regular behavior observed at the whole cell level on the basis of a combined experimental and modeling approach.
| S-EPMC2931296 | biostudies-other
Project description:As one of the ubiquitous second messengers, the intracellular Ca2+, has been revealed to be a pivotal regulator of various cellular functions. Two major sources are involved in the initiation of Ca2+-dependent signals: influx from the extracellular space and release from the intracellular Ca2+ stores such as the endoplasmic/sarcoplasmic reticulum (ER/SR). To manipulate the Ca2+ release from the stores under high spatiotemporal precision, we established a new method termed "organelle optogenetics." That is, one of the light-sensitive cation channels (channelrhodopsin-green receiver, ChRGR), which is Ca2+-permeable, was specifically targeted to the ER/SR. The expression specificity as well as the functional operation of the ER/SR-targeted ChRGR (ChRGRER) was evaluated using mouse skeletal myoblasts (C2C12): (1) the ChRGRER co-localized with the ER-marker KDEL; (2) no membrane current was generated by light under whole-cell clamp of cells expressing ChRGRER; (3) an increase of fluorometric Ca2+ was evoked by the optical stimulation (OS) in the cells expressing ChRGRER in a manner independent on the extracellular Ca2+ concentration ([Ca2+]o); (4) the ΔF/F0 was sensitive to the inhibitor of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and (5) the store-operated Ca2+ entry (SOCE) was induced by the OS in the ChRGRER-expressing cells. Our organelle optogenetics effectively manipulated the ER/SR to release Ca2+ from intracellular stores. The use of organelle optogenetics would reveal the neuroscientific significance of intracellular Ca2+ dynamics under spatiotemporal precision.
| S-EPMC6107701 | biostudies-literature
Project description:Recently developed optogenetic methods promise to revolutionize cell biology by allowing signaling perturbations to be controlled in space and time with light. However, a quantitative analysis of the relationship between a custom-defined illumination pattern and the resulting signaling perturbation is lacking. Here, we characterize the biophysical processes governing the localized recruitment of the Cryptochrome CRY2 to its membrane-anchored CIBN partner. We develop a quantitative framework and present simple procedures that enable predictive manipulation of protein distributions on the plasma membrane with a spatial resolution of 5 ?m. We show that protein gradients of desired levels can be established in a few tens of seconds and then steadily maintained. These protein gradients can be entirely relocalized in a few minutes. We apply our approach to the control of the Cdc42 Rho GTPase activity. By inducing strong localized signaling perturbation, we are able to monitor the initiation of cell polarity and migration with a remarkable reproducibility despite cell-to-cell variability.
| S-EPMC4643200 | biostudies-literature
Project description:Sensory photoreceptors underpin light-dependent adaptations of organismal physiology, development, and behavior in nature. Adapted for optogenetics, sensory photoreceptors become genetically encoded actuators and reporters to enable the noninvasive, spatiotemporally accurate and reversible control by light of cellular processes. Rooted in a mechanistic understanding of natural photoreceptors, artificial photoreceptors with customized light-gated function have been engineered that greatly expand the scope of optogenetics beyond the original application of light-controlled ion flow. As we survey presently, UV/blue-light-sensitive photoreceptors have particularly allowed optogenetics to transcend its initial neuroscience applications by unlocking numerous additional cellular processes and parameters for optogenetic intervention, including gene expression, DNA recombination, subcellular localization, cytoskeleton dynamics, intracellular protein stability, signal transduction cascades, apoptosis, and enzyme activity. The engineering of novel photoreceptors benefits from powerful and reusable design strategies, most importantly light-dependent protein association and (un)folding reactions. Additionally, modified versions of these same sensory photoreceptors serve as fluorescent proteins and generators of singlet oxygen, thereby further enriching the optogenetic toolkit. The available and upcoming UV/blue-light-sensitive actuators and reporters enable the detailed and quantitative interrogation of cellular signal networks and processes in increasingly more precise and illuminating manners.
| S-EPMC6500593 | biostudies-literature
Project description:Optogenetics, a field concentrating on controlling cellular functions by means of light-activated proteins, has shown tremendous potential in neuroscience. It possesses superior spatiotemporal resolution compared to the surgical, electrical, and pharmacological methods traditionally used in studying brain function. A multitude of optogenetic tools for neuroscience have been created that, for example, enable the control of action potential generation via light-activated ion channels. Other optogenetic proteins have been used in the brain, for example, to control long-term potentiation or to ablate specific subtypes of neurons. In in vivo applications, however, the majority of optogenetic tools are operated with blue, green, or yellow light, which all have limited penetration in biological tissues compared to red light and especially infrared light. This difference is significant, especially considering the size of the rodent brain, a major research model in neuroscience. Our review will focus on the utilization of red light-operated optogenetic tools in neuroscience. We first outline the advantages of red light for in vivo studies. Then we provide a brief overview of the red light-activated optogenetic proteins and systems with a focus on new developments in the field. Finally, we will highlight different tools and applications, which further facilitate the use of red light optogenetics in neuroscience.
| S-EPMC8761848 | biostudies-literature
Project description:Due to the rapid economic growth and the heavy reliance on fossil fuels, China has become one of the countries with the highest sulfur dioxide (SO2) emissions, which pose a severe challenge to human health and the sustainable development of social economy. In order to cope with the serious problem of SO2 pollution, this study attempts to explore the spatial temporal variations of industrial SO2 emissions in China utilizing the Defense Meteorological Satellite Program's Operational Linescan System (DMSP-OLS) nighttime stable light (NSL) data. We first explored the relationship between the NSL data and the statistical industrial SO2 emissions at the provincial level, and confirmed that there was a positive correlation between these two datasets. Consequently, 17 linear regression models were established based on the NSL data and the provincial statistical emissions to model the spatial-temporal dynamics of China's industrial SO2 emissions from 1997 to 2013. Next, the NSL-based estimated results were evaluated utilizing the prefectural statistical industrial SO2 emissions and emission inventory data, respectively. Finally, the distribution of China's industrial SO2 emissions at 1 km spatial resolution were estimated, and the temporal and spatial dynamics were explored from multiple scales (national scale, regional scale and scale of urban agglomeration). The results show that: (1) The NSL data can be successfully applied to estimate the dynamic changes of China's industrial SO2 emissions. The coefficient of determination (R2) values of the NSL-based estimation results in most years were greater than 0.6, and the relative error (RE) values were less than 10%, when validated by the prefectural statistical SO2 emissions. Moreover, compared with the inventory emissions, the adjusted coefficient of determination (Adj.R-Square) reached 0.61, with the significance at the 0.001 level. (2) During the observation period, the temporal and spatial dynamics of industrial SO2 emissions varied greatly in different regions. The high growth type was largely distributed in China's Western region, Central region, and Shandong Peninsula, while the no-obvious-growth type was concentrated in Western region, Beijing-Tianjin-Tangshan and Middle south of Liaoning. The high grade of industrial SO2 emissions was mostly concentrated in China's Eastern region, Western region, Shanghai-Nanjing-Hangzhou and Shandong Peninsula, while the low grade mainly concentrated in China's Western region, Middle south of Liaoning and Beijing-Tianjin-Tangshan. These results of our research can not only enhance the understanding of the spatial-temporal dynamics of industrial SO2 emissions in China, but also offer some scientific references for formulating feasible industrial SO2 emission reduction policies.
| S-EPMC7482937 | biostudies-literature