Biophysics of nerve excitation

Experimental studies testifying to the presence of an interrelation between the physiological functions of the organism and physical and chemical processes in nerves are discussed. Changes in some physical and chemical parameters observed both upon elicited rhythmic excitation of nerves and during the spontaneous rhythmic activity of neurons are analyzed. Upon rhythmic excitation, a complex of physical and chemical processes is triggered, and reversible structural and metabolic rearrangements at the subcellular and molecular levels occur that do not take place during the generation of a single action potential. Thus, only in conditions of rhythmic excitation of a nerve, it is possible to reveal those processes that provide excitation of nerves in the organism. The future possibilities of the investigations combining the biophysical and physiological approaches are substantiated. Characteristic changes in physicochemical parameters are observed in nerves during the generation of a series of action potentials of different frequency and duration (“frequency dependence”) under normal physiological conditions, as well as in extreme situations and in nerve pathology. The structural and metabolic rearrangements are directly related to the mode of rhythmic excitation and proceed both in the course of rhythmic excitation and after its termination. Shown also is participation of the basic components of the nervous trunk (axon, Schwann cell, myelin, subcellular organelles) in the realization of rhythmic excitation. In the coordination of all processes involved in rhythmic excitation, the main role is played by the systems of redistribution and transport of intercellular and intracellular calcium. The idea is put forward that myelin of nerve fibers is not only an insulator, but also an “intercellular depot” of calcium and participates in the redistribution of different ions. Thus, the rhythmic excitation is of great importance in the realization of some physiological functions, the adaptation to changing conditions, the liquidation of consequences of paralogical processes, the formation of mechanisms of “memory,” etc.     

Management of time by the cell and by the organism

Time-dependent regulations of cells and organisms can be analysed at different levels. One of these levels is the periodicity of cell functions such as cell division, metabolic processes (generation of ATP by glycolysis or oxidative mitochondrial processes) and the biosynthesis of cell constituents. Studies carried out on unicellular eukaryotes revealed the periodic, oscillatory nature of most of these processes. Time constants of these reactions vary from nanoseconds to hours-days, necessitating coupling mechanisms. Comparative studies revealed the coupling of the rapid processes (mitochondrial ATP generation) to the slower rhythms of the biosynthetic processes of macromolecules. Adenine nucleotides are involved in the coupling mechanisms between rapid and slow processes ("the slow dance of life to the music of time"). The mechanisms underlying these rhythmic processes involve either key allosteric regulatory enzymes (PFK for glycolysis) or "desensitization" of receptors by phosphorylation-dephosphorylation. At the organismic level the study of rhythmic processes is illustrated by the periodicity of heart beats, shown to exhibit multifractality, following apparently the formalism of deterministic chaos. Another example is the rhythmic oscillatory discharges of neuronal networks. The existence of subrhythmes mostly of epigenetic nature, facilitated probably the progressive adjustment of cells during evolution to the slow increase of day time since the separation of the moon from the earth. We analysed the mechanisms underlying the decline of these processes during aging. Loss of receptors or/and their uncoupling from their transmission pathway appear to be involved in most of these processes of decline. One conclusion of this review is the importance of epigenetic mechanisms both in the genesis and in the decline of these rythmic processes involved in time keeping by the cell.     

Circadian variation of cell proliferation in HTR-8/SVneo cell line

Circadian clock controls several physiological processes such as cell proliferation. Extravillous trophoblast proliferation is a tightly regulated function playing a fundamental role in maternal vessel remodeling. We recently demonstrated that clock genes Per2 and Dec1 as well as the clock-controlled genes Dbp and Vegf are rhythmically expressed in human extravillous trophoblast-derived HTR-8/SVneo cells. Analyzing the time course of HTR-8/SVneo cell proliferation, a circadian variation in cell number was found. Moreover, we showed a rhythmic expression of mRNAs for Wee1 and stathmin, two genes involved in cell cycle progression. We suggest that circadian clockwork may orchestrate the functionality of the several factors involved in the control of human trophoblast functions that are fundamental for a successfully pregnancy outcome.     

Rhythmicity of the activity of the supraoptic and paraventricular nuclei of the hypothalamus of the C57Bl mouse

Rhythmical changes in the activity of the neurosecretory processes have been compared in the supraoptic (SON) and paraventricular (PVN) nuclei in the C57Bl mice hypothalamus during vernal equinox. Parts of the neurosecretory cells, being at stages of synthesis, excretion and accumulation of secrete, volumes of the cell nuclei and nucleoli survey as criteria of their activity. Similar feature for the rhythmic of both nuclei studied is the highest activation of the processes during day time, when mice are resting; this is demonstrated as the maximal amount of actively synthesizing cells, maximal volumes of the cell nuclei and nucleoli. The peculiarities of the rhythmic display in the activity is manifested as a greater ability of the SON cells to accumulate neurosecrete. The accumulation of the secretory material in the SON cells precedes to the period of its maximal activity (1-7 PM) characterized: by making the cells free from the secrete and by a maximal increasing the volume of the nucleoli. In the PVN intensified display of the activity is noted at early hours of the day, and the amount of the cells not containing the secrete--at 6 PM. Lack of the neurosecrete accumulation in the PVN cells speaks in favour of more steady than in the SON cells excretion of the secrete. This demonstrates a more even maintenance of neurohormones concentration in the organism.     

节律性听觉刺激下的神经振荡同步化及其应用

大脑的感觉、情绪、认知等功能与其神经振荡模式有密切的联系。通过施加节律性刺激可以调控大脑的神经振荡模式,进而影响个体感受、情绪状态和认知功能等。与近年来常见的非侵入性电刺激和磁刺激相比,同样依赖于外部刺激输入的节律性感觉刺激具有成本低、易操作等优点,被认为是一种极具潜力的神经调控手段。本文以节律性听觉刺激为例,系统综述了不同类型的节律性听觉刺激如何影响大脑的神经振荡模式,进而影响相关状态和功能;并通过总结外部节律性听觉刺激对个体感知觉、情绪与认知功能的影响,讨论其生理机制和应用前景。     

The temporal organization of the complex nodule in the lymph node

The aim of the work is to study rhythmic processes at tissue level in the lymph nodule and in the T-territory adjacent to it in order to reveal temporal interrelations in functioning the germinative center, crown and T-territory. The lymph nodule sections are stained with methylene green-pyronine. Small and middle lymphocytes, immunoblasts, plasmoblasts, immature and mature plasma cells, mitotic figures are taken into account. Spectral composition and rhythmic parameters are determined for each type of the cells in the ultradian, circadian and infradian ranges. Periods, approaching the circadian one, are revealed in the germinative centers for small lymphocytes and immature plasma cells. Practically, for all plasma cells the functional period near to 7 h is found; this attests the presence of the common synchronous rhythm driver. Phase difference of immunoblast, plasmablast, immature plasma cell fluctuation in the germinative centers makes it possible to suppose the time, necessary to transfer the immunoblast into the plasmablast (1.6-2.6 h) and the plasmablast into the immature plasma cell (3 h). Owing to the knowledge of the spectral composition of the rhythmic and parameters of certain components it is possible to approximate the total course of the process. Combination of fluctuations with various periods results in their recurrence in more prolonged time intervals.     

A model of smooth muscle cell synchronization in the arterial wall

Vasomotion is a rhythmic variation in microvascular diameter. Although known for more than 150 years, the cellular processes underlying the initiation of vasomotion are not fully understood. In the present study a model of a single cell is extended by coupling a number of cells into a tube. The simulated results point to a permissive role of cGMP in establishing intercellular synchronization. In sufficient concentration, cGMP may activate a cGMP-sensitive calcium-dependent chloride channel, causing a tight spatiotemporal coupling between release of sarcoplasmic reticulum calcium, membrane depolarization, and influx of extracellular calcium. Low [cGMP] is associated only with unsynchronized waves. At intermediate concentrations, cells display either waves or whole cell oscillations, but these remain unsynchronized between cells. Whole cell oscillations are associated with rhythmic variation in membrane potential and flow of current through gap junctions. The amplitude of these oscillations in potential grows with increasing [cGMP], and, past a certain threshold, they become strong enough to entrain all cells in the vascular wall, thereby initiating sustained vasomotion. In this state there is a rhythmic flow of calcium through voltage-sensitive calcium channels into the cytoplasm, making the frequency of established vasomotion sensitive to membrane potential. It is concluded that electrical coupling through gap junctions is likely to be responsible for the rapid synchronization across a large number of cells. Gap-junctional current between cells is due to the appearance of oscillations in the membrane potential that again depends on the entrainment of sarcoplasmic reticulum and plasma membrane within the individual cell.     

The visual input stage of the mammalian circadian pacemaking system: I. Is there a clock in the mammalian eye?

Threads of evidence from recent experimentation in retinal morphology, neurochemistry, electrophysiology, and visual perception point toward rhythmic ocular processes that may be integral components of circadian entrainment in mammals. Components of retinal cell biology (rod outer-segment disk shedding, inner-segment degradation, melatonin and dopamine synthesis, electrophysiological responses) show self-sustaining circadian oscillations whose phase can be controlled by light-dark cycles. A complete phase response curve in visual sensitivity can be generated from light-pulse-induced phase shifting. Following lesions of the suprachiasmatic nuclei, circadian rhythms of visual detectability and rod outer-segment disk shedding persist, even though behavioral activity becomes arrhythmic. We discuss the converging evidence for an ocular circadian timing system in terms of interactions between rhythmic retinal processes and the central suprachiasmatic pacemaker, and propose that retinal phase shifts to light provide a critical input signal.     

Influence of the feeding regimen on the rhythmicity of the processes of secretion of the supraoptic nucleus in C57Bl mice

During the period of vernal equinox in Leningrad 2 groups of C57Bl male mice have been investigated. Ninety-five animals are given food ecologically adequate at 9 p.m. Eighty-four animals are given foot at 9 a.m.--ecologically inverted regimen of feeding (IRF). The mice are decapitated for 4 days with an interval about 1.5 h. Serial paraffin sections are stained with aldehyde-fuchsin after Gomori and an additional staining of the nuclei with azocarmine. Criteria for the neurosecretory activity is the ratio of the cells amount at various stages of synthesis, outflux and accumulation of the secrete, volumes of the nuclei and nucleoli. Spectrum and parameters of the rhythmicity are revealed. IRF produces decrease in the amount of the ultradian component of the rhythmic parameters, characterizing active synthesis and discharge of the secrete. The part of the neurosecretory cells, those actively synthesizing and discharging the secrete, and volume of the cell nucleoli decrease. Range of ultradian component of the cell part rhythm, depositing the secrete, and the cell volume enriches. Thus, IRF produces certain changes in the rhythmicity of the cell secretion at all the stages: synthesis, discharge and accumulation of the secrete. Total intensity of the synthetic processes decreases. A conclusion is made that IRF inhibits the microsecretory process in the supraoptic nucleus (SON) and decreases adaptive possibilities of its cells. Adaptation to IRF is performed at the expense of rhythmic discharge of neurohormones, deposited in the cells, and at the expense of processes, occurring in the neuryoplasm and resulting in increase of the nuclear volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Visual Benefits in Apparent Motion Displays: Automatically Driven Spatial and Temporal Anticipation Are Partially Dissociated

Many behaviourally relevant sensory events such as motion stimuli and speech have an intrinsic spatio-temporal structure. This will engage intentional and most likely unintentional (automatic) prediction mechanisms enhancing the perception of upcoming stimuli in the event stream. Here we sought to probe the anticipatory processes that are automatically driven by rhythmic input streams in terms of their spatial and temporal components. To this end, we employed an apparent visual motion paradigm testing the effects of pre-target motion on lateralized visual target discrimination. The motion stimuli either moved towards or away from peripheral target positions (valid vs. invalid spatial motion cueing) at a rhythmic or arrhythmic pace (valid vs. invalid temporal motion cueing). Crucially, we emphasized automatic motion-induced anticipatory processes by rendering the motion stimuli non-predictive of upcoming target position (by design) and task-irrelevant (by instruction), and by creating instead endogenous (orthogonal) expectations using symbolic cueing. Our data revealed that the apparent motion cues automatically engaged both spatial and temporal anticipatory processes, but that these processes were dissociated. We further found evidence for lateralisation of anticipatory temporal but not spatial processes. This indicates that distinct mechanisms may drive automatic spatial and temporal extrapolation of upcoming events from rhythmic event streams. This contrasts with previous findings that instead suggest an interaction between spatial and temporal attention processes when endogenously driven. Our results further highlight the need for isolating intentional from unintentional processes for better understanding the various anticipatory mechanisms engaged in processing behaviourally relevant stimuli with predictable spatio-temporal structure such as motion and speech.     

Problems with dimensionless measurement models of synchrony in biological systems

Synchrony is surprisingly complex even in the simplest cases. One strategy for simplifying complex phenomena is to define a dimensionless measurement model with the aim of (1) finding order, (2) comparing complex phenomena, and (3) making decisions about statistical significance. However, a model is only as good as its assumptions. In this paper, several types of dimensionless measurement models of synchrony among biological states are evaluated using the preceding criteria. These dimensionless measurement models are found to be inadequate even in the simplest cases of N individuals cycling through k non-overlapping states. Moreover, independent of their adequacy as measures of synchrony, there is the additional problem of the applicability of biological-state measurement models to rhythmic biological processes. Biological states are often just quantized observations of the phases of rhythmic biological processes. With the help of a concrete example, it is shown that quantizing the phases of a process into discrete states can lead to serious errors. These conclusions do not imply that the study of synchrony in biological systems is intractable. There are statistical approaches for detecting synchrony in groups and researchers are making progress towards understanding the general mechanisms of rhythmic phenomena in biological systems. Am. J. Primatol. 41:65–85, 1997. © 1997 Wiley-Liss, Inc.     

Bifurcation, Bursting, and Spike Frequency Adaptation

Many neural systems display adaptive properties that occur on timescales that are slower than the time scales associated withrepetitive firing of action potentials or bursting oscillations. Spike frequency adaptation is the name givento processes thatreduce the frequency of rhythmic tonic firing of action potentials,sometimes leading to the termination of spiking and the cell becomingquiescent. This article examines these processes mathematically,within the context of singularly perturbed dynamical systems.We place emphasis on the lengths of successive interspikeintervals during adaptation. Two different bifurcation mechanisms insingularly perturbed systems that correspond to the termination offiring are distinguished by the rate at which interspike intervalsslow near the termination of firing. We compare theoreticalpredictions to measurement of spike frequency adaptation in a modelof the LP cell of the lobster stomatogastric ganglion.     

Modeling discrete and rhythmic movements through motor primitives: a review

Rhythmic and discrete movements are frequently considered separately in motor control, probably because different techniques are commonly used to study and model them. Yet the increasing interest in finding a comprehensive model for movement generation requires bridging the different perspectives arising from the study of those two types of movements. In this article, we consider discrete and rhythmic movements within the framework of motor primitives, i.e., of modular generation of movements. In this way we hope to gain an insight into the functional relationships between discrete and rhythmic movements and thus into a suitable representation for both of them. Within this framework we can define four possible categories of modeling for discrete and rhythmic movements depending on the required command signals and on the spinal processes involved in the generation of the movements. These categories are first discussed in terms of biological concepts such as force fields and central pattern generators and then illustrated by several mathematical models based on dynamical system theory. A discussion on the plausibility of theses models concludes the work.     

Stomatal sensing of the environment

The effects of environmental factors on stomatal behaviour are reviewed and the questions of whether photosynthesis and transpiration eontrol stomata or whether stomata themselves control the rates of these processes is addressed. Light affects stomata directly and indirectly. Light can act directly as an energy source resulting in ATP formation within guard cells via photophosphorylation, or as a stimulus as in the case of the blue light effects which cause guard cell H⁺ extrusion. Light also acts indirectly on stomata by affecting photosynthesis which influences the intercellular leaf CO₂ concentration ( C _i). Carbon dioxide concentrations in contact with the plasma membrane of the guard cell or within the guard cell acts directly on cell processes responsible for stomatal movements. The mechanism by which CO₂ exerts its effect is not fully understood but, at least in part, it is concerned with changing the properties of guard cell plasma membranes which influence ion transport processes. The C _i may remain fairly constant for much of the day for many species which is the result of parallel responses of stomata and photosynthesis to light. Leaf water potential also influences stomatal behaviour. Since leaf water potential is a resultant of water uptake and storage by the plant and transpirational water loss, any factor which affects these processes, such as soil water availability, temperature, atmospheric humidity and air movement, may indirectly affect stomata. Some of these factors, such as temperature and possibly humidity, may affect stomata directly. These direct and indirect effects of environmental factors interact to give a net opening response upon which is superimposed a direct effect of stomatal circadian rhythmic activity.     

The study of role of membrane-bound Ca2+ in the regulation of relationship between neuron and glia during rhythmic excitation

The role of membrane-bound Ca2+ in the regulation of Ca2+ transport through voltage-gated Ca2+ channel, and NMDA-glutamate and n-acetylcholine receptors upon interaction of a neuron with glia during rhythmic excitation was studied. It was found that the redistribution and transport of Ca2+ play a crucial role in the conductance of rhythmic excitation in both a "neuron-neuron" system and the processes providing the maintenance of a stationary level of rhythmic excitation in the system "neuron-glia".     

A biophysical approach to the investigation of physiological processes

It was shown that understanding the mechanism of rhythmic excitation in cells and tissues requires the combination of physiological and biophysical approaches. Systemic studies of changes in the physicochemical characteristics of the object were carried out by a protocol that takes into account the mode of rhythmic excitation and the functional sate of the object being studied. The validity of the approach was proved in studies of rhythmic excitation in somatic nonmyelinic and myelinic nerves, and in model systems. The approach can be used in studies of many physiological processes.