Molecular electronics in pinnae of Mimosa pudica

Bioelectrochemical circuits operate in all plants including the sensitive plant Mimosa pudica Linn. The activation of biologically closed circuits with voltage gated ion channels can lead to various mechanical, hydrodynamical, physiological, biochemical and biophysical responses. Here the biologically closed electrochemical circuit in pinnae of Mimosa pudica is analyzed using the charged capacitor method for electrostimulation at different voltages. Also the equivalent electrical scheme of electrical signal transduction inside the plant''s pinna is evaluated. These circuits remain linear at small potentials not exceeding 0.5 V. At higher potentials the circuits become strongly non-linear pointing to the opening of ion channels in plant tissues. Changing the polarity of electrodes leads to a strong rectification effect and to different kinetics of a capacitor. These effects can be caused by a redistribution of K⁺, Cl⁻, Ca²⁺ and H⁺ ions through voltage gated ion channels. The electrical properties of Mimosa pudica were investigated and equivalent electrical circuits within the pinnae were proposed to explain the experimental data.Key words: electrophysiology, plant cell electrostimulation, charged capacitor method, electrical circuits, electrical signaling, Mimosa pudica     

Non-Enhanced MR Imaging of Cerebral Aneurysms: 7 Tesla versus 1.5 Tesla

Purpose

To prospectively evaluate 7 Tesla time-of-flight (TOF) magnetic resonance angiography (MRA) in comparison to 1.5 Tesla TOF MRA and 7 Tesla non-contrast enhanced magnetization-prepared rapid acquisition gradient-echo (MPRAGE) for delineation of unruptured intracranial aneurysms (UIA).

Material and Methods

Sixteen neurosurgical patients (male n = 5, female n = 11) with single or multiple UIA were enrolled in this trial. All patients were accordingly examined at 7 Tesla and 1.5 Tesla MRI utilizing dedicated head coils. The following sequences were obtained: 7 Tesla TOF MRA, 1.5 Tesla TOF MRA and 7 Tesla non-contrast enhanced MPRAGE. Image analysis was performed by two radiologists with regard to delineation of aneurysm features (dome, neck, parent vessel), presence of artifacts, vessel-tissue-contrast and overall image quality. Interobserver accordance and intermethod comparisons were calculated by kappa coefficient and Lin''s concordance correlation coefficient.

Results

A total of 20 intracranial aneurysms were detected in 16 patients, with two patients showing multiple aneurysms (n = 2, n = 4). Out of 20 intracranial aneurysms, 14 aneurysms were located in the anterior circulation and 6 aneurysms in the posterior circulation. 7 Tesla MPRAGE imaging was superior over 1.5 and 7 Tesla TOF MRA in the assessment of all considered aneurysm and image quality features (e.g. image quality: mean MPRAGE7T: 5.0; mean TOF7T: 4.3; mean TOF1.5T: 4.3). Ratings for 7 Tesla TOF MRA were equal or higher over 1.5 Tesla TOF MRA for all assessed features except for artifact delineation (mean TOF7T: 4.3; mean TOF1.5T 4.4). Interobserver accordance was good to excellent for most ratings.

Conclusion

7 Tesla MPRAGE imaging demonstrated its superiority in the detection and assessment of UIA as well as overall imaging features, offering excellent interobserver accordance and highest scores for all ratings. Hence, it may bear the potential to serve as a high-quality diagnostic tool for pretherapeutic assessment and follow-up of untreated UIA.     

Multishot versus single-shot pulse sequences in very high field fMRI: a comparison using retinotopic mapping

High-resolution functional MRI is a leading application for very high field (7 Tesla) human MR imaging. Though higher field strengths promise improvements in signal-to-noise ratios (SNR) and BOLD contrast relative to fMRI at 3 Tesla, these benefits may be partially offset by accompanying increases in geometric distortion and other off-resonance effects. Such effects may be especially pronounced with the single-shot EPI pulse sequences typically used for fMRI at standard field strengths. As an alternative, one might consider multishot pulse sequences, which may lead to somewhat lower temporal SNR than standard EPI, but which are also often substantially less susceptible to off-resonance effects. Here we consider retinotopic mapping of human visual cortex as a practical test case by which to compare examples of these sequence types for high-resolution fMRI at 7 Tesla. We performed polar angle retinotopic mapping at each of 3 isotropic resolutions (2.0, 1.7, and 1.1 mm) using both accelerated single-shot 2D EPI and accelerated multishot 3D gradient-echo pulse sequences. We found that single-shot EPI indeed led to greater temporal SNR and contrast-to-noise ratios (CNR) than the multishot sequences. However, additional distortion correction in postprocessing was required in order to fully realize these advantages, particularly at higher resolutions. The retinotopic maps produced by both sequence types were qualitatively comparable, and showed equivalent test/retest reliability. Thus, when surface-based analyses are planned, or in other circumstances where geometric distortion is of particular concern, multishot pulse sequences could provide a viable alternative to single-shot EPI.     

Signal transduction in Mimosa pudica: biologically closed electrical circuits

Biologically closed electrical circuits operate over large distances in biological tissues. The activation of such circuits can lead to various physiological and biophysical responses. Here, we analyse the biologically closed electrical circuits of the sensitive plant Mimosa pudica Linn. using electrostimulation of a petiole or pulvinus by the charged capacitor method, and evaluate the equivalent electrical scheme of electrical signal transduction inside the plant. The discharge of a 100 µF capacitor in the pulvinus resulted in the downward fall of the petiole in a few seconds, if the capacitor was charged beforehand by a 1.5 V power supply. Upon disconnection of the capacitor from Ag/AgCl electrodes, the petiole slowly relaxed to the initial position. The electrical properties of the M. pudica were investigated, and an equivalent electrical circuit was proposed that explains the experimental data.     

Constraint and Contingency in Multifunctional Gene Regulatory Circuits

Gene regulatory circuits drive the development, physiology, and behavior of organisms from bacteria to humans. The phenotypes or functions of such circuits are embodied in the gene expression patterns they form. Regulatory circuits are typically multifunctional, forming distinct gene expression patterns in different embryonic stages, tissues, or physiological states. Any one circuit with a single function can be realized by many different regulatory genotypes. Multifunctionality presumably constrains this number, but we do not know to what extent. We here exhaustively characterize a genotype space harboring millions of model regulatory circuits and all their possible functions. As a circuit''s number of functions increases, the number of genotypes with a given number of functions decreases exponentially but can remain very large for a modest number of functions. However, the sets of circuits that can form any one set of functions becomes increasingly fragmented. As a result, historical contingency becomes widespread in circuits with many functions. Whether a circuit can acquire an additional function in the course of its evolution becomes increasingly dependent on the function it already has. Circuits with many functions also become increasingly brittle and sensitive to mutation. These observations are generic properties of a broad class of circuits and independent of any one circuit genotype or phenotype.     

NUNDO: a numerical model of a human torso phantom and its application to effective dose equivalent calculations for astronauts at the ISS

The health effects of cosmic radiation on astronauts need to be precisely quantified and controlled. This task is important not only in perspective of the increasing human presence at the International Space Station (ISS), but also for the preparation of safe human missions beyond low earth orbit. From a radiation protection point of view, the baseline quantity for radiation risk assessment in space is the effective dose equivalent. The present work reports the first successful attempt of the experimental determination of the effective dose equivalent in space, both for extra-vehicular activity (EVA) and intra-vehicular activity (IVA). This was achieved using the anthropomorphic torso phantom RANDO^® equipped with more than 6,000 passive thermoluminescent detectors and plastic nuclear track detectors, which have been exposed to cosmic radiation inside the European Space Agency MATROSHKA facility both outside and inside the ISS. In order to calculate the effective dose equivalent, a numerical model of the RANDO^® phantom, based on computer tomography scans of the actual phantom, was developed. It was found that the effective dose equivalent rate during an EVA approaches 700 μSv/d, while during an IVA about 20 % lower values were observed. It is shown that the individual dose based on a personal dosimeter reading for an astronaut during IVA results in an overestimate of the effective dose equivalent of about 15 %, whereas under an EVA conditions the overestimate is more than 200 %. A personal dosemeter can therefore deliver quite good exposure records during IVA, but may overestimate the effective dose equivalent received during an EVA considerably.     

Mechanical and electrical anisotropy in Mimosa pudica pulvini

Thigmonastic or seismonastic movements in Mimosa pudica, such as the response to touch, appear to be regulated by electrical, hydrodynamical and chemical signal transduction. The pulvinus of Mimosa pudica shows elastic properties, and we found that electrically or mechanically induced movements of the petiole were accompanied by a change of the pulvinus shape. As the petiole falls, the volume of the lower part of the pulvinus decreases and the volume of the upper part increases due to the redistribution of water between the upper and lower parts of the pulvinus. This hydroelastic process is reversible. During the relaxation of the petiole, the volume of the lower part of the pulvinus increases and the volume of the upper part decreases. Redistribution of ions between the upper and lower parts of a pulvinus causes fast transport of water through aquaporins and causes a fast change in the volume of the motor cells. Here, the biologically closed electrochemical circuits in electrically and mechanically anisotropic pulvini of Mimosa pudica are analyzed using the charged capacitor method for electrostimulation at different voltages. Changing the polarity of electrodes leads to a strong rectification effect in a pulvinus and to different kinetics of a capacitor discharge if the applied initial voltage is 0.5 V or higher. The electrical properties of Mimosa pudica''s pulvini were investigated and the equivalent electrical circuit within the pulvinus was proposed to explain the experimental data. The detailed mechanism of seismonastic movements in Mimosa pudica is discussed.Key words: electrophysiology, plant electrostimulation, pulvinus, Mimosa pudica, charged capacitor method, electrical circuits, ion channels     

Neuromorphic hardware databases for exploring structure-function relationships in the brain.

Neuromorphic hardware is the term used to describe full custom-designed integrated circuits, or silicon ''chips'', that are the product of neuromorphic engineering--a methodology for the synthesis of biologically inspired elements and systems, such as individual neurons, retinae, cochleas, oculomotor systems and central pattern generators. We focus on the implementation of neurons and networks of neurons, designed to illuminate structure-function relationships. Neuromorphic hardware can be constructed with either digital or analogue circuitry or with mixed-signal circuitry--a hybrid of the two. Currently, most examples of this type of hardware are constructed using analogue circuits, in complementary metal-oxide-semiconductor technology. The correspondence between these circuits and neurons, or networks of neurons, can exist at a number of levels. At the lowest level, this correspondence is between membrane ion channels and field-effect transistors. At higher levels, the correspondence is between whole conductances and firing behaviour, and filters and amplifiers, devices found in conventional integrated circuit design. Similarly, neuromorphic engineers can choose to design Hodgkin-Huxley model neurons, or reduced models, such as integrate-and-fire neurons. In addition to the choice of level, there is also choice within the design technique itself; for example, resistive and capacitive properties of the neuronal membrane can be constructed with extrinsic devices, or using the intrinsic properties of the materials from which the transistors themselves are composed. So, silicon neurons can be built, with dendritic, somatic and axonal structures, and endowed with ionic, synaptic and morphological properties. Examples of the structure-function relationships already explored using neuromorphic hardware include correlation detection and direction selectivity. Establishing a database for this hardware is valuable for two reasons: first, independently of neuroscientific motivations, the field of neuromorphic engineering would benefit greatly from a resource in which circuit designs could be stored in a form appropriate for reuse and re-fabrication. Analogue designers would benefit particularly from such a database, as there are no equivalents to the algorithmic design methods available to designers of digital circuits. Second, and more importantly for the purpose of this theme issue, is the possibility of a database of silicon neuron designs replicating specific neuronal types and morphologies. In the future, it may be possible to use an automated process to translate morphometric data directly into circuit design compatible formats. The question that needs to be addressed is: what could a neuromorphic hardware database contribute to the wider neuroscientific community that a conventional database could not? One answer is that neuromorphic hardware is expected to provide analogue sensory-motor systems for interfacing the computational power of symbolic, digital systems with the external, analogue environment. It is also expected to contribute to ongoing work in neural-silicon interfaces and prosthetics. Finally, there is a possibility that the use of evolving circuits, using reconfigurable hardware and genetic algorithms, will create an explosion in the number of designs available to the neuroscience community. All this creates the need for a database to be established, and it would be advantageous to set about this while the field is relatively young. This paper outlines a framework for the construction of a neuromorphic hardware database, for use in the biological exploration of structure-function relationships.     

Explicit Logic Circuits Predict Local Properties of the Neocortex's Physiology and Anatomy

Background

Two previous articles proposed an explicit model of how the brain processes information by its organization of synaptic connections. The family of logic circuits was shown to generate neural correlates of complex psychophysical phenomena in different sensory systems.

Methodology/Principal Findings

Here it is shown that the most cost-effective architectures for these networks produce correlates of electrophysiological brain phenomena and predict major aspects of the anatomical structure and physiological organization of the neocortex. The logic circuits are markedly efficient in several respects and provide the foundation for all of the brain''s combinational processing of information.

Conclusions/Significance

At the local level, these networks account for much of the physical structure of the neocortex as well its organization of synaptic connections. Electronic implementations of the logic circuits may be more efficient than current electronic logic arrays in generating both Boolean and fuzzy logic.     

Architecture-Dependent Robustness and Bistability in a Class of Genetic Circuits

Understanding the relationship between genotype and phenotype is a challenge in systems biology. An interesting yet related issue is why a particular circuit topology is present in a cell when the same function can supposedly be obtained from an alternative architecture. Here we analyzed two topologically equivalent genetic circuits of coupled positive and negative feedback loops, named NAT and ALT circuits, respectively. The computational search for the oscillation volume of the entire biologically reasonable parameter region through large-scale random samplings shows that the NAT circuit exhibits a distinctly larger fraction of the oscillatory region than the ALT circuit. Such a global robustness difference between two circuits is supplemented by analyzing local robustness, including robustness to parameter perturbations and to molecular noise. In addition, detailed dynamical analysis shows that the molecular noise of both circuits can induce transient switching of the different mechanism between a stable steady state and a stable limit cycle. Our investigation on robustness and dynamics through examples provides insights into the relationship between network architecture and its function.     

The Blood Bank as a Public Health Service

The donation of blood is presented to the public as an altruistic service in which one human helps another. At the same time, the donor receives some help for himself. In the process of blood donation, a medical history is taken, an extremely short physical examination is done, and the donor''s blood is studied by various tests. Although this is by no means the equivalent of a complete physical examination performed by a physician, it sometimes can be helpful in discovering early disease or other medical findings which could be pertinent to the donor''s health.     

Equivalent Circuits as Related to Ionic Systems

The purpose of this paper is to clarify the relationship between certain “equivalent circuits” and the fundamental flux equations of Nernst and Planck. It is shown that as a direct algebraic consequence of these equations one may construct two types of equivalent circuits for a homogeneous (charged or uncharged) membrane. The one, which we term the “pure electrical equivalent circuit,” correctly predicts all of the electrical properties of the membrane for both steady and transient states. The other, which we call the “mixed equivalent circuit,” predicts the steady state I, Ψ characteristics of the membrane and the steady state ionic fluxes; it is not applicable to non-steady state properties or measurements. We emphasize that with regard to the portrayal of the physical basis of the properties of a homogeneous membrane, the mixed equivalent circuit can be misleading. This is particularly significant because this same circuit can also be used to depict a mosaic membrane, in which case the circuit gives a realistic pictorialization of the physical origin of the membrane properties. It is hoped that our analysis will be of aid to workers in electrophysiology who make use of equivalent circuit terminology in discussing the behavior of the plasma membrane.     

Nonlinear equivalent circuits for membranes

The problem of obtaining Helmholtz equivalents for nonlinear resistive one-ports is considered. Two fundamentally different classes of equivalent are described, one local and the other global. For each, necessary and sufficient conditions are derived for the existence and uniqueness of either the Thévenin equivalent or the Norton equivalent or both. These concepts are illustrated (i) by proving that a cell whose channels and pumps are monotone in the membrane potential will, in the absence of net state changes in these ionophores, possess a unique stable resting potential and (ii) by demonstrating that it is in principle impossible to assign unique equivalent circuits to such ionophores.     

In Vivo High-Resolution 7 Tesla MRI Shows Early and Diffuse Cortical Alterations in CADASIL

Background and Purpose

Recent data suggest that early symptoms may be related to cortex alterations in CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic model of cerebral small vessel disease (SVD). The aim of this study was to investigate cortical alterations using both high-resolution T2* acquisitions obtained with 7 Tesla MRI and structural T1 images with 3 Tesla MRI in CADASIL patients with no or only mild symptomatology (modified Rankin’s scale ≤1 and Mini Mental State Examination (MMSE) ≥24).

Methods

Complete reconstructions of the cortex using 7 Tesla T2* acquisitions with 0.7 mm isotropic resolution were obtained in 11 patients (52.1±13.2 years, 36% male) and 24 controls (54.8±11.0 years, 42% male). Seven Tesla T2* within the cortex and cortical thickness and morphology obtained from 3 Tesla images were compared between CADASIL and control subjects using general linear models.

Results

MMSE, brain volume, cortical thickness and global sulcal morphology did not differ between groups. By contrast, T2* measured by 7 Tesla MRI was significantly increased in frontal, parietal, occipital and cingulate cortices in patients after correction for multiple testing. These changes were not related to white matter lesions, lacunes or microhemorrhages in patients having no brain atrophy compared to controls.

Conclusions

Seven Tesla MRI, by contrast to state of the art post-processing of 3 Tesla acquisitions, shows diffuse T2* alterations within the cortical mantle in CADASIL whose origin remains to be determined.     

Robust, high-resolution, whole cell patch-clamp capacitance measurements using square wave stimulation.

High-resolution, whole cell capacitance measurements are usually performed using sine wave stimulation using a single frequency or a sum of two frequencies. We present here a high-resolution technique for whole-cell capacitance measurements based on square-wave stimulation. The square wave represents a sum of sinusoidal frequencies at odd harmonics of the base frequency, the amplitude of which is highest for the base frequency and decreases as the frequency increases. The resulting currents can be analyzed by fitting the current relaxations with exponentials, or by a phase-sensitive detector technique. This method provides a resolution undistinguishable from that of single-frequency sine wave stimulation, and allows for clear separation of changes in capacitance, membrane conductance, and access resistance. In addition, it allows for the analysis of more complex equivalent circuits as associated with the presence of narrow fusion pores during degranulation, tracking many equivalent circuit parameters simultaneously. The method is insensitive to changes in the reversal potential, pipette capacitance, or widely varying cell circuit parameters. It thus provides important advantages in terms of robustness for measuring cell capacitances, and allows analysis of complicated changes of the equivalent circuits.     

A Developmental Switch for Hebbian Plasticity

Hebbian forms of synaptic plasticity are required for the orderly development of sensory circuits in the brain and are powerful modulators of learning and memory in adulthood. During development, emergence of Hebbian plasticity leads to formation of functional circuits. By modeling the dynamics of neurotransmitter release during early postnatal cortical development we show that a developmentally regulated switch in vesicle exocytosis mode triggers associative (i.e. Hebbian) plasticity. Early in development spontaneous vesicle exocytosis (SVE), often considered as ''synaptic noise'', is important for homogenization of synaptic weights and maintenance of synaptic weights in the appropriate dynamic range. Our results demonstrate that SVE has a permissive, whereas subsequent evoked vesicle exocytosis (EVE) has an instructive role in the expression of Hebbian plasticity. A timed onset for Hebbian plasticity can be achieved by switching from SVE to EVE and the balance between SVE and EVE can control the effective rate of Hebbian plasticity. We further show that this developmental switch in neurotransmitter release mode enables maturation of spike-timing dependent plasticity. A mis-timed or inadequate SVE to EVE switch may lead to malformation of brain networks thereby contributing to the etiology of neurodevelopmental disorders.     

Nonlinear electronic circuit with neuron like bursting and spiking dynamics

It is difficult to design electronic nonlinear devices capable of reproducing complex oscillations because of the lack of general constructive rules, and because of stability problems related to the dynamical robustness of the circuits. This is particularly true for current analog electronic circuits that implement mathematical models of bursting and spiking neurons. Here we describe a novel, four-dimensional and dynamically robust nonlinear analog electronic circuit that is intrinsic excitable, and that displays frequency adaptation bursting and spiking oscillations. Despite differences from the classical Hodgkin–Huxley (HH) neuron model, its bifurcation sequences and dynamical properties are preserved, validating the circuit as a neuron model. The circuit's performance is based on a nonlinear interaction of fast–slow circuit blocks that can be clearly dissected, elucidating burst's starting, sustaining and stopping mechanisms, which may also operate in real neurons. Our analog circuit unit is easily linked and may be useful in building networks that perform in real-time.     

Semi-Quantitative vs. Volumetric Determination of Endolymphatic Space in Menière’s Disease Using Endolymphatic Hydrops 3T-HR-MRI after Intravenous Gadolinium Injection

Magnetic resonance imaging enhances the clinical diagnosis of Menière''s disease. This is accomplished by in vivo detection of endolymphatic hydrops, which are graded using different semi-quantitative grading systems. We evaluated an established, semi-quantitative endolymphatic hydrops score and with a quantitative method for volumetric assessment of the endolymphatic size. 11 patients with Menière''s disease and 2 healthy subjects underwent high resolution endolymphatic hydrops 3 Tesla MRI with highly T2 weighted FLAIR and T2DRIVE sequences. The degree of endolymphatic hydrops was rated semi-quantitatively and compared to the results of 3D-volumetry. Moreover, the grade of endolymphatic hydrops was correlated with pure tone audiometry. Semi-quantitative grading and volumetric evaluation of the endolymphatic hydrops are in accordance (r = 0.92) and the grade of endolymphatic hydrops correlates with pure tone audiometry. Patients with a sickness duration of ≥ 30 months showed a significant higher total labyrinth fluid volume (p = 0.03). Fast, semi-quantitative evaluation of endolymphatic hydrops is highly reliable compared to quantitative/volumetric assessment. Endolymphatic space is significantly higher in patients with longer sickness duration.     

Alterations in the rat electrocardiogram induced by stationary magnetic fields

A field strength dependent increase in the amplitude of the T-wave signal in the rat electrocardiogram (ECG) was observed during exposure to homogeneous, stationary magnetic fields. For 24 adult Sprague-Dawley and Buffalo rats of both sexes, the T-wave amplitude was found to increase by an average of 408% in a 2.0 Tesla (1 Tesla = 10⁴ Gauss) field. No significant magnetically induced changes were observed in other components of the ECG record, including the P wave and the QRS complex. The minimum field level at which augmentation of the T wave could be detected was 0.3 Tesla. The magnetically induced increase in T-wave amplitude occurred instantaneously, and was immediately reversible after exposure to fields as high as 2.0 Tesla. No abnormalities in any component of the ECG record, including the T wave, were noted during a period of 3 weeks following cessation of a continuous 5-h exposure of rats to a 1.5-Tesla field. The heart rate and breathing rate of adult rats were not altered during, or subsequent to, application of fields up to 2.0 Tesla. The effect of animal orientation within the field was tested using juvenile rats 3–14 days old. The maximum increase in T-wave amplitude was observed when subjects were placed with the long axis of the body perpendicular to the lines of magnetic induction. These experimental observations, as well as theoretical considerations, suggest that augmentation of the signal amplitude in the T-wave segment of the ECG may result from a superimposed electrical potential generated by aortic blood flow in the presence of a stationary magnetic field.     

Optogenetic Functional MRI

The investigation of the functional connectivity of precise neural circuits across the entire intact brain can be achieved through optogenetic functional magnetic resonance imaging (ofMRI), which is a novel technique that combines the relatively high spatial resolution of high-field fMRI with the precision of optogenetic stimulation. Fiber optics that enable delivery of specific wavelengths of light deep into the brain in vivo are implanted into regions of interest in order to specifically stimulate targeted cell types that have been genetically induced to express light-sensitive trans-membrane conductance channels, called opsins. fMRI is used to provide a non-invasive method of determining the brain''s global dynamic response to optogenetic stimulation of specific neural circuits through measurement of the blood-oxygen-level-dependent (BOLD) signal, which provides an indirect measurement of neuronal activity. This protocol describes the construction of fiber optic implants, the implantation surgeries, the imaging with photostimulation and the data analysis required to successfully perform ofMRI. In summary, the precise stimulation and whole-brain monitoring ability of ofMRI are crucial factors in making ofMRI a powerful tool for the study of the connectomics of the brain in both healthy and diseased states.