Small fly eyes should not see fine image details. Because flies exhibit saccadic visual behaviors and their compound eyes have relatively few ommatidia (sampling points), their photoreceptors would be expected to generate blurry and coarse retinal images of the world. Here we demonstrate that Drosophila see the world far better than predicted from the classic theories. By using electrophysiological, optical and behavioral assays, we found that R1-R6 photoreceptors' encoding capacity in time is maximized to fast high-contrast bursts, which resemble their light input during saccadic behaviors. Whilst over space, R1-R6s resolve moving objects at saccadic speeds beyond the predicted motion-blur-limit. Our results show how refractory phototransduction and rapid photomechanical photoreceptor contractions jointly sharpen retinal images of moving objects in space-time, enabling hyperacute vision, and explain how such microsaccadic information sampling exceeds the compound eyes' optical limits. These discoveries elucidate how acuity depends upon photoreceptor function and eye movements.
Background: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising experimental tool for translational heart research and drug development. However, their usability as a human adult cardiomyocyte model is limited by their functional immaturity. Our aim is to analyse quantitatively those characteristics and how they differ from adult CMs.Methods and Results: We have developed a novel in silico model with all essential functional electrophysiology and calcium handling features of hiPSC-CMs. Importantly, the virtual cell recapitulates the immature intracellular ion dynamics that are characteristic for hiPSC-CMs, as quantified based our in vitro imaging data. The strong “calcium clock” is a source for a dual function of excitation-contraction coupling in hiPSC-CMs: action potential and calcium transient morphology vary substantially depending on the activation sequence of underlying ionic currents and fluxes that is altered in spontaneous vs. paced mode. Furthermore, parallel simulations with hiPSC-CM and adult cardiomyocyte models demonstrate the central differences. Results indicate that hiPSC-CMs translate poorly the disease specific phenotypes of Brugada syndrome, long QT Syndrome and catecholaminergic polymorphic ventricular tachycardia, showing less robustness and greater tendency for arrhythmic events than adult CMs. Based on a comparative sensitivity analysis, hiPSC-CMs share some features with adult CMs, but are still functionally closer to prenatal CMs than adult CMs. A database analysis of 3000 hiPSC-CM model variants suggests that hiPSC-CMs recapitulate poorly fundamental physiological properties of adult CMs. Single modifications do not appear to solve this problem, which is mostly contributed by the immaturity of intracellular calcium handling.Conclusion: Our data indicates that translation of findings from hiPSC-CMs to human disease should be made with great caution. Furthermore, we established a mathematical platform that can be used to improve the translation from hiPSC-CMs to human, and to quantitatively evaluate hiPSC-CMs development toward more general and valuable model for human cardiac diseases.
When developing large-scale mathematical models of physiology, some reduction in complexity is necessarily required to maintain computational efficiency. A prime example of such an intricate cell is the cardiac myocyte. For the predictive power of the cardiomyocyte models, it is vital to accurately describe the calcium transport mechanisms, since they essentially link the electrical activation to contractility. The removal of calcium from the cytoplasm takes place mainly by the Na C /Ca 2C exchanger, and the sarcoplasmic reticulum Ca 2C ATPase (SERCA). In the present study, we review the properties of SERCA, its frequency-dependent and b-adrenergic regulation, and the approaches of mathematical modelling that have been used to investigate its function. Furthermore, we present novel theoretical considerations that might prove useful for the elucidation of the role of SERCA in cardiac function, achieving a reduction in model complexity, but at the same time retaining the central aspects of its function. Our results indicate that to faithfully predict the physiological properties of SERCA, we should take into account the calcium-buffering effect and reversible function of the pump. This 'uncomplicated' modelling approach could be useful to other similar transport mechanisms as well.
Ideally, neuronal functions would be studied by performing experiments with unconstrained animals whilst they behave in their natural environment. Although this is not feasible currently for most animal models, one can mimic the natural environment in the laboratory by using a virtual reality (VR) environment. Here we present a novel VR system based upon a spherical projection of computer generated images using a modified commercial data projector with an add-on fish-eye lens. This system provides equidistant visual stimulation with extensive coverage of the visual field, high spatio-temporal resolution and flexible stimulus generation using a standard computer. It also includes a track-ball system for closed-loop behavioural experiments with walking animals. We present a detailed description of the system and characterize it thoroughly. Finally, we demonstrate the VR system’s performance whilst operating in closed-loop conditions by showing the movement trajectories of the cockroaches during exploratory behaviour in a VR forest.
BackgroundThe cardiomyocyte is a prime example of inherently complex biological system with inter- and cross-connected feedback loops in signalling, forming the basic properties of intracellular homeostasis. Functional properties of cells and tissues have been studied e.g. with powerful tools of genetic engineering, combined with extensive experimentation. While this approach provides accurate information about the physiology at the endpoint, complementary methods, such as mathematical modelling, can provide more detailed information about the processes that have lead to the endpoint phenotype.ResultsIn order to gain novel mechanistic information of the excitation-contraction coupling in normal myocytes and to analyze sophisticated genetically engineered heart models, we have built a mathematical model of a mouse ventricular myocyte. In addition to the fundamental components of membrane excitation, calcium signalling and contraction, our integrated model includes the calcium-calmodulin-dependent enzyme cascade and the regulation it imposes on the proteins involved in excitation-contraction coupling. With the model, we investigate the effects of three genetic modifications that interfere with calcium signalling: 1) ablation of phospholamban, 2) disruption of the regulation of L-type calcium channels by calcium-calmodulin-dependent kinase II (CaMK) and 3) overexpression of CaMK. We show that the key features of the experimental phenotypes involve physiological compensatory and autoregulatory mechanisms that bring the system to a state closer to the original wild-type phenotype in all transgenic models. A drastic phenotype was found when the genetic modification disrupts the regulatory signalling system itself, i.e. the CaMK overexpression model.ConclusionThe novel features of the presented cardiomyocyte model enable accurate description of excitation-contraction coupling. The model is thus an applicable tool for further studies of both normal and defective cellular physiology. We propose that integrative modelling as in the present work is a valuable complement to experiments in understanding the causality within complex biological systems such as cardiac myocytes.
Insect ocelli are relatively simple eyes that have been assigned various functions not related to pictorial vision. In some species they function as sensors of ambient light intensity, from which information is relayed to various parts of the nervous system, e.g., for the control of circadian rhythms. In this work we have investigated the possibility that the ocellar light stimulation changes the properties of the optomotor performance of the cockroach Periplaneta americana. We used a virtual reality environment where a panoramic moving image is presented to the cockroach while its movements are recorded with a trackball. Previously we have shown that the optomotor reaction of the cockroach persists down to the intensity of moonless night sky, equivalent to less than 0.1 photons/s being absorbed by each compound eye photoreceptor. By occluding the compound eyes, the ocelli, or both, we show that the ocellar stimulation can change the intensity dependence of the optomotor reaction, indicating involvement of the ocellar visual system in the information processing of movement. We also measured the cuticular transmission, which, although relatively large, is unlikely to contribute profoundly to ocellar function, but may be significant in determining the mean activity level of completely blinded cockroaches.
The information transfer rate provides an objective and rigorous way to quantify how much information is being transmitted through a communications channel whose input and output consist of time-varying signals. However, current estimators of information content in continuous signals are typically based on assumptions about the system's linearity and signal statistics, or they require prohibitive amounts of data. Here we present a novel information rate estimator without these limitations that is also optimized for computational efficiency. We validate the method with a simulated Gaussian information channel and demonstrate its performance with two example applications. Information transfer between the input and output signals of a nonlinear system is analyzed using a sensory receptor neuron as the model system. Then, a climate data set is analyzed to demonstrate that the method can be applied to a system based on two outputs generated by interrelated random processes. These analyses also demonstrate that the new method offers consistent performance in situations where classical methods fail. In addition to these examples, the method is applicable to a wide range of continuous time series commonly observed in the natural sciences, economics and engineering.
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