Method for constructing the boundary of the bursting oscillations region in the neuron model.

We examine the problem of constructing the boundary of bursting oscillations on a parameter plane for the system of equations describing the electrical behaviour of the membrane neuron arising from the interaction of fast oscillations of the cytoplasma membrane potential and slow oscillations of the intracellular calcium concentration. As the boundary point on the parameter plane we consider the values at which the limit cycle of the slow subsystem is tangent to the Hopf bifurcation curve of the fast subsystem. The method suggested for determining the boundary is based on the dissection of the system variables into slow and fast. The strong point of the method is that it requires the integration of the slow subsystem only. An example of the application of the method for the stomatogastric neuron model [Guckenheimer J, Gueron S, Harris-Warrick RM (1993) Philos Trans R Soc Lond B 341: 345-359] is given.

Activity of foot skin mechanoreceptors and afferent nerve fibres in the adult rat sciatic nerve are altered after central axotomy of sensory neurons.

The functional properties of skin mechanoreceptors were examined in the hind foot of normal rats in comparison with animals subjected to dorsal rhizotomy. Evoked nerve impulses were recorded from afferent nerve fibres of the tibial nerve. The decentralized mechanoreceptors displayed evidence of autonomous functioning, but with several abnormalities as compared to normal animals. There was a decreased sensitivity to mechanical stimulation and a lower adaptive capacity as a consequence of rhizotomy. The underlying mechanism is suggested to be a loss of central trophic support because of the interrupted link between the central nervous system and the sensory ganglion cell periphery. The findings indicate that mechanical receptors continue functioning under conditions when sensory impulses flow cannot reach postsynaptic target neurons in the central nervous system, but stop at the level of the primary sensory neuron.

Cl- transport in the lobster stretch receptor neurone.

Experiments were performed to identify mechanisms underlying non-leakage and non-H+/HCO3--linked transmembrane Cl- transports in the slowly adapting stretch receptor neurone of the European lobster, using intracellular microelectrode and pharmacological techniques. In methodological tests, it was established that direct estimates of intracellular Cl- with ion-sensitive microelectrodes are statistically identical with indirect estimates by means of a GABA method, where 1-2 mM GABA is transforming the cell's membrane voltage into its Cl- equilibrium voltage from which the Cl- concentration is inferred by the Nernst equation. From experiments using sodium orthovanadate and ethacrynic acid, supposed to block primary Cl- pumps, and bumetanide, supposed to block Na-K-Cl co-transporters, it appeared that neither of the two Cl- transport systems exists in the stretch receptor neurone. It could be shown, however, that the cell is equipped with an electroneutral K-Cl co-transporter that (a) is blockable by furosemide in high (Km approximately 350 microM), by 4-acetamido-4'-isothiocyanato-stilbene-2,2-disulphonic acid (SITS) in medium-high (Km approximately 35 microM), and by 4, 4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS) in low (Km approximately 15 microM) doses, (b) is (transiently) activatable by (1 mM) n-ethylmaleimide, (c) is not suppressed by extracellular Rb+ or NH4+, and (d) is not directly coupled to any transmembrane transports of Na+, H+ or HCO3-. From functional tests, with varying transmembrane K+ and Cl- gradients, evidence obtained that the K-Cl co-transporter is able to reverse its transport direction and to adjust its transport rate in a considerable range. As a whole, the results speak in favour of the K-Cl co-transporter being responsible (a) for normally keeping the intracellular Cl- concentration at low levels, for an optimization of the cell's inhibitory system, and (b) for achieving fast transmembrane shifts of K+ (and Cl-), as a means of stabilizing the cell's membrane excitability in conditions of varying extracellular K+ concentrations.

Changes in afferent impulse activity of small intestine mesenteric nerves in response to antigen challenge.

Sprague-Dawley rats (weight 130-150 g) were sensitized by an intraperitoneal injection of 1 mg chicken egg albumin with 0.25 ml Freund's adjuvant to stimulate immunoglobulin E antibody production. Leukocyte migration inhibitory factor was used as an indicator of animal sensitization. In acute electrophysiological experiments on sensitized animals, an intra-arterial or intraluminal chicken egg albumin (100 microg) challenge evoked a 10% enhancement of the activity of mesenteric nerves of the small intestine, regardless of the injection site chosen. Afferent nerve activity in control animals was not changed during the chicken egg albumin challenge. Morphometry at the light microscope level showed activation of mast cell degranulation after the antigen challenge to presensitized rats. Intraluminal injections of a stimulator of mast cell degranulation, compound 48/80 (20-30 mg), were found to increase afferent discharges in intact rats. An antagonist of H1 histamine receptors, clemastine, reduced the effect of compound 48/80. The results obtained provide direct evidence for the stimulation of sensory nerve endings by mast cell mediators released during mast cell degranulation.

[Functional characteristics of foot skin mechanoreceptors and afferent nerve fibers of the sciatic nerve after central axotomy of sensory neurons]. / Issledovanie funktsional'nykh kharakteristik retseptorov kozhi stopy i afferentnykh nervnykh volokon sedalishchnogo nerva krysy posle tsentral'noi aksotomii sensornykh neironov.

The activity of mechanoreceptors was studied in normal rats' hindfoot and compared with that of rhizotomised animals. Evoked nerve impulses were recorded from afferent fibres of the n.tibialis. A possible autonomous functioning of decentralised mechanoreceptors, even though in an altered fashion, was shown. The registered shifts comprised a decrease in sensitivity to mechanical stimulation and lower adaptive properties. The findings suggest that the underlying mechanism involves a probable lack of trophic interaction leading to interruption of a link between the CNS and the peripheral nervous system.

[The protective effect of the nerve growth factor in exposing a nerve tissue culture to diphtheria toxin]. / Protektivnyi éffekt faktora rosta nervov pri vozdeistvii difteriinogo toksina na kul'turu nervnoi tkani.

Diphtheria toxin (1.10(-1)-1.10(-6) Lf/ml) was found to inhibit neurite extension in chick embryo dorsal root ganglia in vitro. If the nerve growth factor (60 ng/ml) was added with toxin in culture media the diphtheria toxin effect was decreased and the neurite outgrowth was compared with control. Protective effect of nerve growth factor by influence of diphtheria toxin may be used in new principles of diphtheria treatment.

Sensory processing in the pallium of a mormyrid fish.

To investigate the functional organization of higher brain levels in fish we test the hypothesis that the dorsal gray mantle of the telencephalon of a mormyrid fish has discrete receptive areas for several sensory modalities. Multiunit and compound field potentials evoked by auditory, visual, electrosensory, and water displacement stimuli in this weakly electric fish are recorded with multiple semimicroelectrodes placed in many tracks and depths in or near telencephalic area dorsalis pars medialis (Dm). Most responsive loci are unimodal; some respond to two or more modalities. Each modality dominates a circumscribed area, chiefly separate. Auditory and electrical responses cluster in the dorsal 500 micrometer of rostral and caudolateral Dm, respectively. Two auditory subdivisions underline specialization of this sense. Mechanoreception occupies a caudal area overlapping electroreception but centered 500 micrometer deeper. Visual responses scatter widely through ventral areas. Auditory, electrosensory, and mechanosensory responses are dominated by a negative wave within the first 50 msec, followed by 15-55 Hz oscillations and a slow positive wave with multiunit spikes lasting from 200 to 500 msec. Stimuli can induce shifts in coherence of certain frequency bands between neighboring loci. Every electric organ discharge command is followed within 3 msec by a large, mainly negative but generally biphasic, widespread corollary discharge. At certain loci large, slow ("deltaF") waves usually precede transient shifts in electric organ discharge rate. Sensory-evoked potentials in this fish pallium may be more segregated than in elasmobranchs and anurans and have some surprising similarities to those in mammals.

Effect of low-intensity millimeter-range electromagnetic irradiation on the recovery of function in lesioned sciatic nerves in rats.

The effects of electromagnetic irradiation (EMI) of wavelength 5.6 mm (frequency 53.57 GHz) and power density 4 mW/cm2 on the recovery of function in damaged rat sciatic nerve were studied; damage was produced by nerve section followed by microsuturing. Irradiation was applied to the skin of the thigh in the area of suturing. Total action potential (TAP) recording from the nerve was used to study the functional properties of regenerating nerve fibers five months after lesioning. These experiments demonstrated that EMI had a stimulatory effect on regenerative processes in the nerve, in terms of 25-30% increases in the rate of action potential conduction along nerve fibers, with increases in TAP amplitude.

Effect of veratridine on the release of neurotrophic factors in nerve tissue cultures.

The depolarizing agent veratridine was shown to affect the level of neurotrophic substances in combined cultures of neonatal rat hippocampus and chick embryo spinal ganglia. In this experimental model, the level of neurotrophic factors in rat hippocampus explants increased as a result of increases in neuronal activity mediated by veratridine. The effects of these neurotrophins on neurite growth in the sensitive spinal ganglion neurons in the combined cultures were evaluated using morphometric methods. Neurite-stimulating effects were seen when veratridine was added to the nutritive medium at a concentration of 90 nM. Antibody to nerve growth factor blocked the action of veratridine. These results demonstrate a role for neuron activity as a regulatory mechanism controlling the expression of neurotrophins.

Role of neurotrophic factors in adaptational processes of the nervous system.

Neurotrophic factors (NTF) are low-molecular-weight proteins which epigenetically determine neuron survival during embryogenesis and the maintenance of their morphofunctional properties in the adult organism. NTF are located in mesenchymal tissues and reach neuron bodies by means of retrograde axoplasmic transport in nerve fibers; in cell bodies, NTF increase anabolic activity, neurotransmitter synthesis, and structural protein production. Neuron cell bodies have two types of specialized receptors for binding the most common NTF, nerve growth factor (NGF). In the brain, NGF does not affect adrenergic neurons, as it does in the periphery, but acts on cholinergic neurons in the basal part of the forebrain. The forebrain plays the major role in the processes of learning, memory, and plasticity, i.e., in the entire complex of adaptational responses of the nervous system, and these may thus depend on the biological activities of substances, including NTF, in forebrain tissues. An experimental model was developed consisting of organotypic co-cultivation of rat hippocampus fragments with chick embryo dorsal root ganglia. This model was used to demonstrate that epileptiform activity in the hippocampus is associated with increases in NTF release, which can be regarded as an adaptive compensatory response to nerve cell damage occurring during convulsive activity.

[The effect of activated macrophage products on neurite growth in an organotypic culture of chick embryo sensory ganglia]. / Vliianie produktov aktivirovannykh makrofagov na rost neiritov v organotipicheskoi kul'ture chuvstvitel'nykh gangliev kurinykh émbrionov.

Murine peritoneal macrophages, activated by BCG vaccine, and human peripheral blood monocytes, activated by lipopolysaccharides, exerted neurite stimulating or neurite inhibiting effects in various periods of activation. The supernatants of these preparations were active in organotypic culture of chick embryo dorsal root ganglia. The inhibition of neurite growth on the 1st day of cultivation was followed by the neurite-stimulating effect. The fluctuation of neurite-inhibition and neurite-stimulation effect of macrophage supernatants suggest the availability of certain changes in cytokine composition in different periods of macrophage activation.

[Effect of RB-101, inhibitor of enkephalin degrading enzymes, on recovery of conductivity of the injured sciatic nerve in rats]. / Vliianie RB-101, blokatora fermentov, razrushaiushchikh énkefaliny, na vosstanovlenie provodimosti povrezhdennogo sedalishchnogo nerva krysy.

A dose-dependent effect of the enkephalinase RB-101 on functional recovery of the rat injured sciatic nerve was revealed. The findings suggest the enkephalines participation in regulation of regenerative processes in peripheral nerves.

Epileptiform activity increases the level of nerve growth factor in cerebrospinal fluid of epileptic patients and in hippocampal neurons in tissue culture.

A neurite-stimulating effect was induced by both the cerebrospinal fluid of epileptic patients and the media of co-cultures of rat hippocampus and chick embryo sensory neurons after veratridine treatment. Cerebrospinal fluid from patients with epilepsy stimulated extensive neurite growth in the organotypic culture of chick embryo dorsal root ganglia. The anti-nerve growth factor antibody partly blocked the neurite-stimulating effect of the cerebrospinal fluid. Co-cultures of newborn rat hippocampus and chick embryo dorsal root ganglia were used to investigate the involvement of neurotrophic factors into the processes which are activated by neuronal activity. The data obtained suggest that veratridine, an epileptiform agent, gave rise to an elevation in the level of neurotrophic factors in the culture media and neurite outgrowth of dorsal root ganglia sensory neurons. The anti-nerve growth factor antibody was shown to block the neurite-stimulating effect mediated by veratridine. These results indicate that the epileptiform activity of neurons evokes the expression of neurotrophins.

Mast cell mediators excite the afferents of cat small intestine.

The influence of intra-arterial injections of 5-hydroxytryptamine, histamine and prostaglandin E2 on afferent impulse activity of mesenteric nerves of small intestine was studied. In anaesthetized cats 5-hydroxytryptamine (10(-5)-10(-4) M) and histamine (10(-5)-10(-3) M) were shown to increase the impulse activity in a dose-dependent manner. Metergolin, 5-hydroxytryptamine antagonist, suppressed the effect of 5-hydroxytryptamine. Clemastine and cimetidine, antagonists of H1 and H2 histamine receptors respectively, distinctly diminished excitatory histamine effects. Prostaglandin E2 (10-30 micrograms/kg) enhanced the afferent impulse activity. The results suggest that afferents of the small intestine may be involved in reception of inflammatory and immune responses.

[The effect of the mast-cell mediators histamine and prostaglandins on the afferent nerve fibers of the small intestine in the cat]. / Vliianie mediatorov tuchnykh kletok gistamina i prostaglandinov na afferentnye nervnye volokna tonkoi kishki koshki.

Histamine was shown to increase afferent impulse activity of the small intestine's mesenteric nerves in a dose-dependent manner, the effect being reduced by antagonists of the H1 and H2 histamine receptors. PG E2 and PC D2 also enhanced the afferent impulse activity. Interaction of antigens with the intestinal mast cells seems to participate in immune response.

Effect of low-intensity millimeter wave electromagnetic radiation on regeneration of the sciatic nerve in rats.

The effect of low-intensity millimeter wave electromagnetic radiation (MWR) on regeneration of the rat sciatic nerve after transection and microsurgical reapproximation was examined. Rats were exposed to 54 GHz MWR at a power density of 4 mW/cm2. It was found that MWR treatment of the femoral skin in the area of suture accelerated the regeneration of nerve fibers. At the twentieth postoperative day, the MWR-treated animals had a 32% increase in the regeneration distance compared to the control animals. The conduction velocity showed a 26% increase in the MWR-treated animals.

[The effect of veratridine on the release of neurotrophic factors in a nerve tissue culture]. / Vliianie veratridina na vydelenie neirotroficheskikh faktorov v kul'ture nervnoi tkani.

A depolarising agent veratridine was shown to affect the level of neurotrophic substances in a combined culture of the newborn rats hippocampus and chick embryo spinal ganglia: the growth of sprouts of the ganglia's sensitive neurons was enhanced. The effect seems to be mediated by the veratridine effect on the hippocampal neurons. The role of an increased level of neurotrophic factors in an increase of neuronal activity, is discussed.