The epileptic neuron: I

Mathematical models of neurons are studied which exhibit spontaneous and repetitive firings in the absence of normally occurring substances. The activity of such neurons could result in the symptoms of epilepsy. The identification of such substances would be important in the treatment of the disease as well as in the understanding of their mode of action. The importance of the geometrical and physical parameters for the generation of spontaneous repetitive discharges is brought out.     

Acontine-induced repetitive firing in frog skeletal muscle and the effect on cable properties

The repetitive firing in curarized frog sartorius muscle caused by aconitine was found to be associated with a dose-dependent membrane depolarization and a decrease in membrane resistance (R_m). Shortly after aconitine treatment, when repetitive discharges began to occur spontaneously in a few fibers (the pre-burst state), the muscle fibers were hypersensitive to mechanical and electrical stimulation. After a repetitive discharge (the post-burst state), the membrane potential fell to the 40–50 mV range. Cable measurements demonstrated that R_m decreased by 27% in the pre-burst state and by 47% in the post-burst state. Substitution of choline for sodium in the post-burst state restored the membrane potential to normal and raised the R_m toward the control level. It is proposed that aconitine's production of repetitive discharges in skeletal muscle is partly the result of maintaining the sodium conductance g_Na at a higher-than-normal level once excitation has been initiated.     

Coerulospinal enhancement of repetitive firing with correlative changes in postspike afterhyperpolarization of cat spinal motoneurons

The present study was aimed at determining if inputs from the locus coeruleus (LC) have any effect on repetitive firing of ventral horn motoneurons in cats. In hindlimb flexor and extensor motoneurons stimulated intrasomatically with current below the threshold for repetitive discharges, added LC-evoked excitatory post-synaptic potentials (EPSPs) were consistently found to produce repetitive firing, suggesting a lowering in the repetitive firing threshold attributable to excitatory LC inputs. With those extensor motoneurons showing episodic, self-sustained firing, LC-EPSPs introduced during the quiescent period were capable of starting a continuous discharge with rhythmic frequencies higher than the spontaneous activity. In some of these cells, intracellularly applied hyperpolarizing current was able to stop the spontaneous discharges. Subsequently, LC stimuli were found to reinitiate repetitive discharges, thus counteracting the ongoing suppression of the motoneurons. Quantitative analysis of the single-spike afterhyperpolarization (AHP) indicated a consistent reduction in its amplitude and time course (duration, time-to-peak, half-decay time) for flexor and extensor motoneurons in response to LC conditioning stimuli. Present results suggest an excitatory LC action on the repetitive discharges of cat motoneurons accompanied by a concurrent decrease in the amplitude and time course of the single-spike AHPs.     

刺激家兔扣带回前部对丘脑腹后外侧核痛敏神经元放电的作用

131只家兔在三碘季铵酚麻痹下,用玻璃微电极在腹后外侧核(VPL)记录对伤害性刺激有反应的单位。在786个 VPL 单位中,对伤害性刺激有反应的单位共128个,占总数16.3%.其中116今对伤害性刺激呈兴奋效应,占90.6%。其余12个呈抑制效应,占9.4%。静脉注射吗啡可以取消这些神经元对伤害性刺激的放电反应。78次的测试结果表明扣带回前部的刺激可以抑制32%VPL 神经元的自发放电活动。同样,也可以抑制由于伤害性刺激而引起的 VPL 神经元的放电反应。这种抑制程度和扣带回的刺激频率有关;8Hz 的刺激频率所引起的抑制效应最佳。上述实验结果说明,扣带回可以通过其下行纤维的活动;影响伤害性冲动在丘脑 VPL水平上的传递。     

Synaptic mechanisms of use-dependent potentiation and use-dependent inhibition of evoked burst discharges in rat hippocampal slices

The mechanisms of activity-dependent modulation of burst discharges in rat hippocampal slices have been studied. The extracellular registration of field responses (population spike, PS, and field excitatory postsynaptic potential, fEPSP) induced by repetitive electrical stimulation (1–4 Hz) of Schaffer collaterals (with 30 pulses trains separated by 5-min resting intervals) was performed in cellular and dendritic layers of CA1 area. It has been established that repetitive orthodromic stimulation exerts biphasic modulation of burst discharges in Mg²⁺-free medium: use-dependent potentiation (UDP) and use-dependent inhibition (UDI). The former was manifested as an increase in the number of PS in the burst discharge associated with a corresponding lengthening of the fEPSP. During the UDI development the number of NMDA-dependent PS in the burst was diminished despite the continuing increase in the fEPSP duration. In some cases UDI was followed by spreading depression. Both UDP and UDI were reversible. The development of UDP and UDI could be effectively suppressed either by the NMDA antagonists or by the GABAergic inhibition enhancer, diazepam. The picrotoxin (PTX)-induced burst discharges did not undergo either UDP or UDI development. However, removal of Mg²⁺ from PTX-containing solution during continuing repetitive stimulation led to the appearance of NMDA-dependent UDI. Analysis of the data obtained indicates that: (1) UDP results from a progressive decrease in GABA-mediated inhibition in the course of low-frequency (1–4 Hz) repetitive stimulation (the so-called “fatigue of synaptic inhibition”); (2) UDI is caused by excessive Ca²⁺ influx into the neurons due to overactivation of NMDA receptors. The article is published in the original.     

Neuromuscular transmission in cultures of adult human and rodent skeletal muscle after innervation in vitro by fetal rodent spinal cord

Electrophysiologic analyses have been carried out on in vitro-coupled explants of fetal rodent spinal cord and adult skeletal muscle of human as well as rodent origin. The studies demonstrate that characteristic neuromuscular transmission can develop and be maintained in these unusual tissue combinations during long-term culture. After coupling periods of 2–7 weeks in vitro, selective stimulation of spinal cord evokes widespread coordinated contractions in the muscle tissue. Simultaneous microelectrode recordings of cord and muscle responses to local cord, or ventral root, stimuli show that muscle action potentials (and contractions) generally occur with latencies of several msec after onset of cord discharges. Similar temporal relations are often seen during spontaneous rhythmic discharges of the coupled cord and muscle tissues. Long series of repetitive discharges, at 2–5 sec intervals, may occur synchronously between these cord and muscle explants, in response to single cord (or dorsal-root ganglion) stimuli, and they may also appear spontaneously. d-Tubocurarine (1–10 μg/ml) selectively and reversibly blocks neuromuscular transmission in these cultures. Eserine accelerates recovery of normal function. Spontaneous repetitive fibrillations of many of the cultured muscle fibers are observed sporadically, and these contractions often continue unabated after block of neuromusclar transmission by d-tubocurarine. Many of the fibers which show asynchronous fibrillations are probably not innervated (as in denervated muscle in situ). In some cases, however, extracellular as well as intracellular recordings indicate that similar fibrillations may also occur in fibers which are clearly innervated. Repetitive cord and muscle discharges are greatly augmented after introduction of strychnine. Complex rhythmic oscillatory (ca. 10/sec) afterdischarges generated in strychninized cord explants lead to similarly patterned muscle discharges (and contractions), which may also occur, at, times, in normal medium.     

Generation of Very Slow Neuronal Rhythms and Chaos Near the Hopf Bifurcation in Single Neuron Models

We have presented a new generation mechanism of slow spiking or repetitive discharges with extraordinarily long inter-spike intervals using the modified Hodgkin-Huxley equations (Doi and Kumagai, 2001). This generation process of slow firing is completely different from that of the well-known potassium A-current in that the steady-state current-voltage relation of the neuronal model is monotonic rather than the N-shaped one of the A-current. In this paper, we extend the previous results and show that the very slow spiking generically appears in both the three-dimensional Hodgkin-Huxley equations and the three dimensional Bonhoeffer-van der Pol (or FitzHugh-Nagumo) equations. The generation of repetitive discharges or the destabilization of the unique equilibrium point (resting potential) is a simple Hopf bifurcation. We also show that the generation of slow spiking does not depend on the stability of the Hopf bifurcation: supercritical or subcritical. The dynamics of slow spiking is investigated in detail and we demonstrate that the phenomenology of slow spiking can be categorized into two types according to the type of the corresponding bifurcation of a fast subsystem: Hopf or saddle-node bifurcation.     

Responses of neurons in cat primary somatosensory cortex to repetitive stimulation of vibrissae

Extra- and intracellular responses of neurons in the primary somatosensory cortex to repetitive mechanical stimulation of the vibrissae at different frequencies were studied in unanesthetized curarized adult cats. Unlike responses to electrical stimulation of the combined afferent input (the infraorbital nerve) spike discharges of neurons in response to vibrissal stimulation can reproduce rather higher frequencies of stimulation and their initial character changes more often in the course of the repetitive series. Most cortical neurons were characterized by limitation of the area of their peripheral receptive fields with an increase in the frequency of adequate repetitive stimulation. A group of cortical neurons was distinguished by its ability to respond to high-frequency stimulation and to generate burst discharges. Comparison of the frequency characteristics of spike responses of these cells and of inhibitory synaptic action in other cortical neurons led to the conclusion that this group of cells thus distinguished may be inhibitory cortical neurons. The role of interaction between excitatory and inhibitory processes arising in cortical neurons during repetitive stimulation of different areas of their receptive fields is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 14, No. 2, pp. 164–171, March–April, 1982.     

Responses of cells in the somatosensory cortex of unanaesthetized cats after sinusoidal displacements of single vibrissae

Summary Neurones in the somatosensory cortex of unanaesthetized restrained cats were recorded during single trapezoid and repetitive sinusoidal displacements of single vibrissae. Responses to trapezoid displacements were similar to those described previously in anaesthetized cats (Hellweg et al., 1977).During repetitive mechanical stimulation cortical cells showed adaptive behaviour so that at higher stimulation frequencies the number of cell discharges per stimulus cycle decreased. The ability to follow the repetition of the stimulus at a one to one ratio was lost in the frequency range between 20 Hz and 60 Hz. A few exceptional cells, while not following at a one to one ratio, still showed some periodicities in their response histograms corresponding to repetition rates of up to 100 Hz. In about 10% of the cells nonmonotonic functions between stimulation frequency and response per cycle were found. These nonmonotonic functions as well as the different adaptive behaviour of cells could not be predicted on the basis of their response to trapezoid stimuli.Measurements of the phase differences between stimulus cycle and response peaks during repetitive stimulation showed that both can vary as a function of stimulation frequency. It is discussed whether these findings could be compatible with the concept of phase coding in the somatosensory cortex.     

A model of Martian surface chemistry

Summary Alkaline earth and alkali metal superoxides and peroxides,-Fe₂O₃ and carbon suboxide polymer are proposed to be constituents of the Martian surface material. These reactive substances explain the water modified reactions and thermal behaviors of the Martian samples demonstrated by all of the Viking Biology Experiments. It is also proposed that the syntheses of these substances result mainly from electrical discharges between wind-mobilized particles at Martian pressures; plasmas are initiated and maintained by these discharges. Active species in the plasma either combine to form or react with inorganic surfaces to create the reactive constitutents.     

Evaluating environmental sustainability with the Waste Absorption Footprint (WAF): An application in the Taihu Lake Basin,China

The ecological footprint (EF) is an accepted worldwide method for the evaluation of environmental sustainability. However, its utility is limited by the existence of a series of shortcomings in the methodology such as the only-partial inclusion of human generated wastes. To improve the ability of the footprint method to evaluate environmental sustainability, a new footprint-based indicator – the ‘Waste Absorption Footprint’ (WAF) – has been proposed. The purpose of this paper is to test this methodological approach by evaluating the sustainability of the water environment in the Taihu Lake Basin, in densely populated eastern China. Applying the WAF method indicates that anthropogenic discharges of wastes have imposed an absorption pressure on the local water system such that the local water environment is increasingly unsustainable. Furthermore, nitrogen and phosphorus are identified as more critical wastes than organic substances, while domestic discharges are shown to be more important sources compared with those from industry and agriculture, which therefore should be the focus of environmental management and pollution control initiatives. It is demonstrated that the WAF method can provide a wealth of information that can be used for reference by local water environmental management authorities.     

甲醚菊酯和溴氰菊酯在果蝇幼虫外周神经系统的协同毒理作用

本文运用细胞内微电极记录技术研究了甲醚菊酯和溴氰菊酯对果蝇Drosophila melanogaster幼虫神经一肌肉突触兴奋性接点电位(EJP₅)的影响。用甲醚菊酯(1.49x10^-8m01/L)处理后引起果蝇EJP₅的自发释放增加和刺激后的重复后自发释放。而用溴氰菊酯(1.0x10^-8mol/L)处理的则无明显影响。这显示甲醚菊酯对果蝇外周神经主要为I型毒理作用。而溴氰菊酯则主要为Ⅱ型作用,甲醚菊酯和溴氰菊酯联合应用后,则产生兼具I型和II型特征的自发释放或诱发EJP₅发放。自发释放或重复后自发释放的频率和幅值随联合处理中甲醚菊脂和溴氰菊酯的配比而变化。这些结果说明甲醚菊酯和溴氰菊酯对果蝇幼虫外周神经的毒理具有协同作用。     

Development of spinal cord bioelectric activity in spinal chick embryos and its behavioral implications

Embryonic behavior of the chick is the product of spontaneous multiunit burst discharges within the ventral spinal cord. The present study describes the ontogeny of spinal cord burst discharges in embryos which were deprived of brain input by removing several neural tube segments of 2-day embryos at cervical or mid-thoracic levels. Characteristics of bioelectric activity present in both intact and chronically transected cords are: (a) the appearance of spike discharges; (b) the organization of unit discharges into synchronized multiunit bursts; (c) the establishment of intracord synchronization of burst discharges over wide expanses of cord tissue; (d) an increase in burst duration and complexity at 7 days due to the appearance of the burst afterdischarge; (e) an increase in the amount of burst activity from 6 to 13 days followed by a decline until hatching at 21 days; (f) a shift from periodic to irregular patterns of burst activity at 13 days; and (g) the existence of the cord burst discharge as a correlate of embryonic movement. Several differences were found between burst activity from chronic spinal and intact embryos: (a) cervical spinal embryos were significantly less active than controls from 15 through 19 days; and (b) long sequences of unusual repetitive burst afterdischarges appeared in chronic spinal embryos by 13 days. The results indicate that the transected embryonic spinal cord is remarkably autogenous in function, although patterns of activity unique to the transected cord appear and increase in prominence during later stages of incubation.     

Coding of information by the olfactory receptor cells of the antenna of Camponotus vagus

The antennal olfactory receptors of the ant Camponotus vagus can qualitatively and quantitatively discriminate between several organic substances which are tested at their maximum vapour pressure (at 22°C). Repetitive stimulation by the same substance evokes unitary discharges which exhibit either sensitization or adaptation. The influence of the cell's autoactivity on the pattern of firing is also discussed.The responses given by one cell stimulated by different substances at the same concentration are described: if the substances have an identical chemical function, the quantitative parameters of firing are generally correlated with respective p.m.; for the others, it is possible to define a differential efficacy order for each substance in the cell. This order varies with the cell, but it is not modified by the cell's autoactivity. Different concentrations of the same substance give responses whose frequency and duration become that much more important as the concentration is high (Figs. 14 and 15).Reaction delay is also a function of concentration. These effects can be modified by spontaneous activity of the cell.     

Spiking properties of olfactory receptor cells in the slice preparation

The whole-cell, patch clamp [corrected] method was applied to olfactory receptor cells in slice preparations made from bullfrog olfactory epithelium. Under voltage-clamp conditions, olfactory receptor cells showed a transient inward current followed by a steady outward current in response to depolarizing voltage steps, as has been shown in the isolated preparation. The input resistance was 5.4 +/- 3.9 GOmega and capacitance 21.9 +/- 9.7 pF. Under current-clamp conditions, depolarization of cells by current injection induced action potentials. In 13 out of 20, spike generation was repetitive with a maximum frequency of 24 Hz. The frequency of the repetitive discharges increased as the injected current was increased. The relationship between the size of the injected current and firing frequency could be well fitted by the Michaelis-Menten equation, indicating that the spike generation site lacks the non-linear boosting system. The slice preparation developed here would provide a powerful tool to study the spike encoding system of the olfactory receptor cells.     

调制多觉型伤害性感受器持续放电的体液因素

利用复合致痛剂引起大鼠皮肤多觉型伤害性感受器(PMN)持续放电的模型,发现刺激坐骨神经中枢端对 PMN 持续放电有显著的抑制或先易化后抑制效应。通过交叉灌流,刺激供血动物的坐骨神经也可对受血动物的 PMN 持续放电产生类似的效应。注射刺激坐骨神经动物的血清,可显著影响 PMN 的活动。大部分单位的抑制效应不被纳洛酮翻转。对吗啡耐受的动物,刺激坐骨神经仍可引起抑制效应。预先利血平化,则使刺激的易化效应基本取消。结果证实,躯体神经传入冲动诱发体液因素调制 PMN 的持续性活动。其中参与抑制效应的因子可能有阿片类与非阿片类,参与易化效应的因子可能是儿茶酚胺。     

The tarso-pretarsal chordotonal organ as an element in cockroach walking

Many types of sense organs have been demonstrated to show repetitive discharges during walking that could provide informational cues about leg movements and other parameters of locomotion. We have recorded activities of receptors of the distal (tarsal) segments of the cockroach hindleg in restrained and freely moving animals while they were videotaped. These recordings show peaks of activities at the onset and termination of the stance phase. We have morphologically and physiologically identified a joint angle receptor, the tarso-pretarsal chordotonal organ, that contributes to the discharges seen late in stance, prior to the onset of leg flexion in swing. This sense organ encodes the angle and rate of change of the most distal leg joint and specifically discharges when the claws are disengaged from the substrate. Applied displacements of the claws in restrained preparations elicit reflex activation of the tibial flexor muscle and a crossed extensor reflex in the opposite hindleg. These reflexes could function to insure that leg flexion in swing does not occur until the claws are disengaged and to enhance support by the opposite hindleg. Thus, the regular discharges of the chordotonal organ could assure efficient and coordinated muscle contractions and movements during normal, unperturbed walking. Accepted: 2 January 1997     

Suggestions for a mathematical model of a pathological neuron with spontaneous repetitive discharges

A formal mathematical model is proposed for a spontaneously repetitively firing neuron. It is based on the assumption that an excitatory and inhibitory substance, possibly different from those involved in synaptic transmissions, is formed in the soma of everynormal neuron. Furthermore, the decay of the substances is ascribed to their combination with some other substances, present in healthy individuals. A generalized two factor system of differential equations is used. It is shown that when the normally present substances are absent, possibly due to genetic defects so that the decay constants become zero, the equations lead to undamped sinusoidal solutions of the difference between excitatory and inhibitory factors, thus producing a trulyspontaneous repetitive discharge, in the absence of external currents or other stimulation. It is suggested that convulsants may act by destroying the substances present in healthy individuals. It is further suggested that by administering to epileptics those substances, which are present in normal healthy persons, perhaps by using brain extracts fromhealthy higher animals which sometimes suffer from epilepsy, an actual cure rather than symptomatic treatment by anticonvulsants may be obtained.     

视前区微量注射吗啡对大鼠丘脑束旁核痛反应神经元电活动的影响

本实验观察了视前区(POA)内微量注入阿片样物质对丘脑束旁核(Pf)痛反应神经元电活动影响。结果如下:(1)POA 内微量注射高浓度吗啡(10μg/μl)能显著抑制 Pf 内大部分(20/26)痛兴奋神经元(PEN)的痛诱发放电,其中3个神经元注药后对伤害性刺激转变成抑制反应;POA 内微量注射低浓度吗啡(1μg/μl)也显著抑制 Pf 内大部分(19/23)PEN 的痛诱发放电。(2) POA 内微量注射两种浓度的吗啡,均使大多数痛抑制神经元(PIN,共27/33)的完全抑制时程缩短。上述结果提示,POA 内阿片样物质对 Pf 内痛反应神经元的电活动可能具有抑制作用。