Gravity sensing in the central nervous system

For human based space research it is of high importance to understand the influence of gravity on the properties of the central nervous system (CNS). Untill now it is not much known about how neuronal tissue can sense gravity. The aim of this study was to find out weather and how the CNS, as a complex system, can percept and react to changes in gravity. Neuronal tissue and especially the CNS fulfils all the requirements for excitable media. Consequently, self-organisation, pattern formation and propagating excitation waves as typical events of excitable media have been observed in such tissue. The Spreading Depression (SD), an excitation depression wave is the most obvious and best described of these phenomena in the CNS. In our experiments we showed that the properties of the SD and therefore the CNS in its properties as an excitable medium reacts very sensitive to changes in gravity.     

Development of one experimental module to study the modulation of the propagation velocity of chemical excitation waves in gel by weak external force (gravity)

Biological and chemical systems in which the pattern of flow of energy and matter imposes self-organization can be seen as examples of excitable media. One property of such media is the presence of excitation waves. The Belouzov-Zabotinsky(B-Z) reaction system and the retinal spreading depression wave are examples of experimental models of excitable media in which the influence of gravity can be studied. In this paper we describe one especial module constructed to test the influence of gravity in gels of the B-Z system. In the gel condition, convection effects are minimized. The results will be directly comparable to retinal experiments programmed by the same group and complete a series of investigations of systematic comparison of the modulation of chemical and biological excitation waves by weak external forces.     

Spiral waves of spreading depression in the isolated chicken retina

Existence of the theoretically predicted spiral waves of excitation in intact two-dimensional networks of excitable elements has been experimentally confirmed in the isolated chicken retina. The preparation supports the waves of Leão's spreading depression (SD) the concentric propagation of which from the point of origin can be directly observed as a change of the optical properties of the retinal tissue. The propagation rate of 3.7 mm/min (35°C) decreased to 1.5 mm/min for SD waves elicited during relative refractory period. When a several-mm long segment of the SD wave had been blocked by anodal polarization, the laterally opened ends of the wavefront started to spread after termination of polarization into the previously blocked tissue, gradually turning around and penetrating into the region recovering from the original SD. One or two simultaneously generated spiral waves of SD continued to rotate for several cycles. Spiral SD could also be elicited by punctiform cathodal polarization (1 mA) applied to the SD wave-rear. Since the new SD wave could only spread into the recovering tissue it formed a laterally open wavefront, the free ends of which eventually turned around and started spiral SD. With continued reverberation the nucleus of the spiral SD wave gradually migrated across the retina until it approached an obstacle (e.g., pecten) which stopped further spiral propagation. Spiral SD waves were elicited in 31 retinal preparations and lasted for 4.5 cycles on the average. Average cycle duration was 4.7 min. Spontaneous spiral SD waves were observed in preparations incubated in Mg²⁺-free media. The spiral SD waves in retina are compared with mathematical models of analogous phenomena. It is argued that spiral SD waves probably exist in the cerebral cortex of rats and account for generation of repetitive SD waves sometimes elicited by overlapping stimulation of two cortical regions.     

Image processing techniques applied to excitation waves in the chicken retina

Image processing techniques are described in detail that are used to gain information about the dynamics of wave propagation in excitable media. We focus on a phenomenon called spreading depression (SD) observed in the chicken retina, but the techniques described here concern a large variety of excitable systems. Despite the impressive progress both in SD research of the past 50 years and, during nearly the same period, in the theory of self-organization of wave patterns, there is still little mutual overlap. However, the increasing demands for understanding complex systems, like neuronal tissue, require such theoretical concepts. Arguments are given why the chicken retina is a nearly perfect experimental system for assessing and further developing these concepts.     

Collision of two action potentials in a single excitable cell

BackgroundIt is a common incident in nature, that two waves or pulses run into each other head-on. The outcome of such an event is of special interest, because it allows conclusions about the underlying physical nature of the pulses. The present experimental study dealt with the head-on meeting of two action potentials (AP) in a single excitable plant cell (Chara braunii internode).MethodsThe membrane potential was monitored with multiple sensors along a single excitable cell. In control experiments, an AP was excited electrically at either end of the cell cylinder. Subsequently, stimuli were applied simultaneously at both ends of the cell in order to generate two APs that met each other head-on.ResultsWhen two action potentials propagated into each other, the pulses did not penetrate but annihilated (N = 26 experiments in n = 10 cells).ConclusionsAPs in excitable plant cells did not penetrate upon meeting head-on. In the classical electrical model, this behavior is specifically attributed to relaxation of ion channel proteins. From an acoustic point of view, annihilation can be viewed as a result of nonlinear material properties (e.g. a phase change).General significanceThe present results suggest that APs in excitable animal and plant cells belong to a similar class of nonlinear phenomena. Intriguingly, other excitation waves in biology (intracellular waves, cortical spreading depression, etc.) also annihilate upon collision and are thus expected to follow the same underlying principles as the observed action potentials.     

Calcium signalling in glial cells

Calcium signals are the universal way of glial responses to the various types of stimulation. Glial cells express numerous receptors and ion channels linked to the generation of complex cytoplasmic calcium responses. The glial calcium signals are able to propagate within glial cells and to create a spreading intercellular Ca2+ wave which allow information exchange within the glial networks. These propagating Ca2+ waves are primarily mediated by intracellular excitable media formed by intracellular calcium storage organelles. The glial calcium signals could be evoked by neuronal activity and vice versa they may initiate electrical and Ca2+ responses in adjacent neurones. Thus glial calcium signals could integrate glial and neuronal compartments being therefore involved in the information processing in the brain.     

The myogenic component in distention-induced peristalsis in the guinea pig small intestine

In an in vitro model for distention-induced peristalsis in the guinea pig small intestine, the electrical activity, intraluminal pressure, and outflow of contents were studied simultaneously to search for evidence of myogenic control activity. Intraluminal distention induced periods of nifedipine-sensitive slow wave activity with superimposed action potentials, alternating with periods of quiescence. Slow waves and associated high intraluminal pressure transients propagated aborally, causing outflow of content. In the proximal small intestine, a frequency gradient of distention-induced slow waves was observed, with a frequency of 19 cycles/min in the first 1 cm and 11 cycles/min 10 cm distally. Intracellular recording revealed that the guinea pig small intestinal musculature, in response to carbachol, generated slow waves with superimposed action potentials, both sensitive to nifedipine. These slow waves also exhibited a frequency gradient. In addition, distention and cholinergic stimulation induced high-frequency membrane potential oscillations (~55 cycles/min) that were not associated with distention-induced peristalsis. Continuous distention produced excitation of the musculature, in part neurally mediated, that resulted in periodic occurrence of bursts of distally propagating nifedipine-sensitive slow waves with superimposed action potentials associated with propagating intraluminal pressure waves that caused pulsatile outflow of content at the slow wave frequency.     

On architectures of circuits implemented in simulated Belousov-Zhabotinsky droplets

When lipid vesicles filled with Belousov-Zhabotinsky (BZ) excitable chemical medium are packed in tight assembles, waves of excitation may travel between the vesicles. When several waves meet in a vesicle some fragments may deflect, others can annihilate or continue their travel undisturbed. By interpreting waves as Boolean values we can construct logical gates and assemble them in large circuits. In numerical modelling we show two architectures of one-bit half-adders implemented in BZ-vesicles.     

Interstitial potentials and their change with depth into cardiac tissue.

The electrical source strength for an isolated, active, excitable fiber can be taken to be its transmembrane current as an excellent approximation. The transmembrane current can be determined from intracellular potentials only. But for multicellular preparations, particularly cardiac ventricular muscle, the electrical source strength may be changed significantly by the presence of the interstitial potential field. This report examines the size of the interstitial potential field as a function of depth into a semi-infinite tissue structure of cardiac muscle regarded as syncytial. A uniform propagating plane wave of excitation is assumed and the interstitial potential field is found based on consideration of the medium as a continuum (bidomain model). As a whole, the results are inconsistent with any of the limiting cases normally used to represent the volume conductor, and suggest that in only the thinnest of tissue (less than 200 micron) can the interstitial potentials be ignored.     

Physiological studies of cortical spreading depression

Cortical spreading depression (CSD) produces propagating waves of transient neuronal hyperexcitability followed by depression. CSD is initiated by K+ release following neuronal firing or electrical, mechanical or chemical stimuli. A triphasic (30-50 s) cortical potential transient accompanies localized transmembrane redistributions of K+, glutamate, Ca2+, Na+, Cl- and H+. Accumulated K+ in the restricted interstitial space can cause both further neuronal depolarisation and inward movement of K+ into astrocytes that buffers this increased extracellular K+ concentration ([K+])o. However, astrocyte interconnections may then propagate the CSD wave by K+ liberation through an opening of remote K+ channels by volume, Ca2+ or N-methyl-D-aspartate receptor activation. Changes in cerebral blood volume and in apparent water diffusion co-efficient (ADC) accompanying CSD were first studied using magnetic resonance imaging (MRI) in whole lissencephalic brains. Diffusion-weighted echoplanar imaging in gyrencephalic brains went on to demonstrate CSD features that paralleled classical migraine aura. The ADC activity persisted minutes/hours post KCl stimulus. Pixelwise analyses distinguished single primary events and multiple, spatially restricted, slower propagating, secondary events whose detailed features varied with the nature of the originating stimulus. These ADC changes varied reciprocally with T2*-weighted (i.e. referring to spin-spin relaxation times) waveforms reflecting local blood flow. There followed prolonged decreases in cerebral blood flow culminating in late cerebrovascular changes blocked by the antimigraine agent sumatriptan. CSD phenomena have possible translational significance for human migraine aura and other cerebral pathologies such as the peri-infarct depolarisation events that follow ischaemia and brain injury.     

Negative Tension of Scroll Wave Filaments and Turbulence in Three-Dimensional Excitable Media and Application in Cardiac Dynamics

Scroll waves are vortices that occur in three-dimensional excitable media. Scroll waves have been observed in a variety of systems including cardiac tissue, where they are associated with cardiac arrhythmias. The disorganization of scroll waves into chaotic behavior is thought to be the mechanism of ventricular fibrillation, whose lethality is widely known. One possible mechanism for this process of scroll wave instability is negative filament tension. It was discovered in 1987 in a simple two variables model of an excitable medium. Since that time, negative filament tension of scroll waves and the resulting complex, often turbulent dynamics was studied in many generic models of excitable media as well as in physiologically realistic models of cardiac tissue. In this article, we review the work in this area from the first simulations in FitzHugh–Nagumo type models to recent studies involving detailed ionic models of cardiac tissue. We discuss the relation of negative filament tension and tissue excitability and the effects of discreteness in the tissue on the filament tension. Finally, we consider the application of the negative tension mechanism to computational cardiology, where it may be regarded as a fundamental mechanism that explains differences in the onset of arrhythmias in thin and thick tissue.     

Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons

Neurogenesis is known to persist in the adult mammalian central nervous system (CNS). The identity of the cells that generate new neurons in the postnatal CNS has become a crucial but elusive issue. Using a transgenic mouse, we show that NG2 proteoglycan-positive progenitor cells that express the 2',3'-cyclic nucleotide 3'-phosphodiesterase gene display a multipotent phenotype in vitro and generate electrically excitable neurons, as well as astrocytes and oligodendrocytes. The fast kinetics and the high rate of multipotent fate of these NG2+ progenitors in vitro reflect an intrinsic property, rather than reprogramming. We demonstrate in the hippocampus in vivo that a sizeable fraction of postnatal NG2+ progenitor cells are proliferative precursors whose progeny appears to differentiate into GABAergic neurons capable of propagating action potentials and displaying functional synaptic inputs. These data show that at least a subpopulation of postnatal NG2-expressing cells are CNS multipotent precursors that may underlie adult hippocampal neurogenesis.     

Properties of spreading depression during different phases of cyclic excitation of the rat neocortex

Properties of cortical spreading depression were studied during different phases of cyclic excitation developing in the neocortex of rats under the influence of low-frequency electrical stimulation. Waves of spreading depression appeared in the cortex spontaneously or after microinjection of potassium chloride. During each excitation cycle a state preventing the passage and appearance of these waves developed in the region of electrical stimulation. The degree of blocking in other areas of the cortex outside the region of stimulation depended on the distance from the site of electrical stimulation and on generalization of excitatation over the cortex. After the end of the excitation phase, while the current continued to act, the ability of the cortex to conduct the depression wave was restored. In intervals of cyclic excitation the duration of the waves of spreading depression remained on average only half its duration in the absence of stimulation. The time course of development and the character of recovery of depression during the intervals confirm the hypothesis that activation of the potassium-sodium pump may have a role in the blocking mechanism and enable the temporal parameters of this process to be estimated.     

Finding paths in a labyrinth based on reaction-diffusion media.

During the past few decades, many proposals were made on how to take an effective solution for finding a path in a labyrinth, one of the most well known problems of high computational complexity inherent in information processing by biomolecular and biological entities. In particular, attempts were made to use a technique attractive enough for solving this problem based on wave processes in reaction-diffusion media. Trigger waves in reaction diffusion systems spread simultaneously through all paths of the labyrinth in a highly parallel mode. Regretfully, the velocity of these waves is extremely low which gave no way for the practical implementation of this technique until now. An effective 'hardware' system was designed which was capable of finding a path in a labyrinth using fast phase waves. Three principal points were assumed as a basis for this design, i.e. (1) hybrid architecture that combined an information processing reaction-diffusion medium which performs operations of high computational complexity with a digital computer carrying out supplementary image processing operations; (2) light-sensitive information processing media of Belousov-Zhabotinsky type that enables the simulation of the labyrinth and spreading wave evolution by their images stored in the medium and reduces the problem to the image processing operations; (3) fast light-induced phase wave processes that spreads through the labyrinth in several seconds instead of hours which is typical for trigger waves inherent in reaction-diffusion media. These fundamentals along with the additional procedure of testing for labyrinth fragment connectness provided us with the opportunity to solve labyrinth problems.     

Long-range Ca2+ waves transmit brain-damage signals to microglia

Microglia are the resident phagocytes of the brain that are responsible for the clearance of injured neurons, an essential step in subsequent tissue regeneration. How death signals are controlled both in space and time to attract these cells toward the site of injury is a topic of great interest. To this aim, we have used the optically transparent zebrafish larval brain and identified rapidly propagating Ca2+ waves that determine the range of microglial responses to neuronal cell death. We show that while Ca2+-mediated microglial responses require ATP, the spreading of intercellular Ca2+ waves is ATP independent. Finally, we identify glutamate as a potent inducer of Ca2+-transmitted microglial attraction. Thus, this real-time analysis reveals the existence of a mechanism controlling microglial targeted migration to neuronal injuries that is initiated by glutamate and proceeds across the brain in the form of a Ca2+ wave.     

The emergence of wave emitting centres in an excitable medium

The response of an excitable biological medium to a double local stimulus is considered within the context of a mathematical model for a layer of starving cells of Dictyostelium discoideum, with both spatially one- and two-dimensional (1D and 2D) system being investigated. In contrast to the response usually seen in excitable media, whereby each superthreshold stimulus delivered to the relaxed medium results in the initiation of just one travelling wave, a source emitting a sequence of waves can develop in the present excitable medium after the second stimulus. In a 1D system, only transient wave sources forming a limited number of waves are found. In 2D systems, a permanent wave sources consisting in a pair of spirals are observed as well as the transient wave sources forming circular wave patterns. The general features of the medium dynamics that underlie the observed responses to the double stimulus are discussed.     

On Propagation of Excitation Waves in Moving Media: The FitzHugh-Nagumo Model

Background

Existence of flows and convection is an essential and integral feature of many excitable media with wave propagation modes, such as blood coagulation or bioreactors.

Methods/Results

Here, propagation of two-dimensional waves is studied in parabolic channel flow of excitable medium of the FitzHugh-Nagumo type. Even if the stream velocity is hundreds of times higher that the wave velocity in motionless medium (), steady propagation of an excitation wave is eventually established. At high stream velocities, the wave does not span the channel from wall to wall, forming isolated excited regions, which we called “restrictons”. They are especially easy to observe when the model parameters are close to critical ones, at which waves disappear in still medium. In the subcritical region of parameters, a sufficiently fast stream can result in the survival of excitation moving, as a rule, in the form of “restrictons”. For downstream excitation waves, the axial portion of the channel is the most important one in determining their behavior. For upstream waves, the most important region of the channel is the near-wall boundary layers. The roles of transversal diffusion, and of approximate similarity with respect to stream velocity are discussed.

Conclusions

These findings clarify mechanisms of wave propagation and survival in flow.     

Effect of local depression of inhibition on electrical activity of the spinal cord

The dorsal cord, dorsal root, and focal potentials in response to peripheral nerve stimulation were investigated in rats with local depression of inhibition in the left or right half of the lumbar segments produced by the action of tetanus toxin. The investigation was carried out at the stage of poisoning when excitation of the neuron population with disturbed inhibition caused generalized excitation of spinal and bulbar motoneurons. Experiments on spinal animals showed that if a cutaneous nerve is stimulated on the side affected by the toxin these responses have a greater amplitude and a much longer duration than those evoked by stimulation of the opposite nerve or responses in healthy rats. The maximal increase in amplitude and duration of the negative component of the focal potential corresponding to the time of the increased P wave of the dorsal cord potential was found in the ventral quadrant on the side affected by the toxin. Besides evoked focal potentials, spontaneous rhythmic negative waves also were recorded in this area. The mechanisms of spread of seizure activity from the focus of depressed inhibition are discussed and the structures generating spreading seizure activity are identified.