The effect of acute alcoholization on the neuronal activity of the normal ventromedial hypothalamus and in pharmacological actions on the brain monoaminergic and opiate systems]

In experiments on white outbred male rats the specificity was studied of the influence and mechanisms of action of acute alcoholization (30%-solution of ethanol, intraperitoneally, 0.7 g/kg) on the activity of functionally different neurones of the ventromedial hypothalamus. Experimental results showed that the neurones, the activity of which lowered after saturation (I-st type), increased the discharges frequency at administration of ethanol. Nerve cells, the activity of which increased (II-nd type) and did not change (III-nd type) after saturation, had inhibitory character of reaction in response to alcoholization. The increase of serotonin content in the brain elicited by intraperitoneal administration of 5-OTPh (50 mg/kg) blockaded the action of ethanol on the nerve cells of the I-st type and did not change the effect of the alcohol on the neurones of the II-nd and III-nd types. Preliminary lowering of the noradrenaline level in the brain (disulphiram, intraperitoneally, 100 mg/kg) and blockade of opiate receptors (nalorphine, 5 mg/kg) fully eliminated ethanol influence on the activity of all types of neurones.     

Reflection of the plastic properties of the simplest neuronal associations in statistical characteristics of the spike activity of their elements. Polysynaptically linked neurons

Changes of crosscorrelation histograms of trains of action potentials and mean interspike intervals of polysynaptically connected neurones were studied by means of mathematical modelling of synaptic neuronal interaction at changes of efficiency of interneuronal monosynaptic connections, at changes of neuronal excitability, and at changes of total action on them of independent disorderly afferent synaptic inflows. Increase of amplitude of the main maximum (minimum) of the normalized crosscorrelation histogram of trains of action potentials accompanied by reduction of mean interspike intervals of both neurones, was shown to be a unsignificant indication of an increase of efficiency of polysynaptic excitatory (inhibitory) connections between the neurones (due to modification of synapses or to a change of the functional state of interneurones).     

The role of dopamine and serotonin in modulating the defensive behavior of the edible snail

Dopamine application in concentration of 10(-5)-10(-6) M into saline around the snail CNS leads to decrease of excitability of LPa7 neurone which is presynaptic in relation to defensive behaviour command neurones, and to decrease of amplitude of monosynaptic excitatory postsynaptic potential (EPSP) in the command neurones elicited by intracellular stimulation of LPa7 neurone. Besides, the dopamine causes a decrease of summated EPSP amplitude in the studied neurones in response to intestinal nerve stimulation (70% in average), a change of rest potential towards hyperpolarization for 6-8 mV, a reduction of the command neurones input resistance (20% in average). The described influences can lead to a general increase of the threshold of defensive system reaction to stimulation. Dopamine action on the defensive behaviour command neurones is significantly weakened in serotonine presence. Against the dopamine background, the efficiency of serotonine influence on the value of EPSP in command neurones in response to testing stimulus is reduced. According to the obtained data, a conclusion is made that interrelation of dopamine and serotonine concentrations can be a base for formation of behaviour choice in snail.     

A comparative analysis of the effect of an analog of vasopressin on functionally different neurons in the grape snail

Application of desglycine-argininvasopressin (DG-AVP) differently influenced different types of cells of snail isolated central nervous system. In neurosecretory cells an increase of spontaneous impulse activity took place and, as a rule, bursts of impulses appeared, most often of synaptic origin, excluding PPa1 neurones and one of the neurosecretory cells of the left parietal ganglion. The increase of the bursts activity in these cells was based on the increase of the amplitude of membrane potential waves. Under the influence of neurosecretory cells system activation, EPSPs frequency and amplitude in secondary-sensory neurones increased, which led to a greater probability of the action potentials appearance. At prolonged action the spontaneous EPSPs in these cells began to group in bursts. Excitability and membrane resistance of these cells remained unchanged. DG-AVP had no influence on primary-sensory neurones and motoneurones.     

Depression of presynaptic excitation by the activation of vanilloid receptor 1 in the rat spinal dorsal horn revealed by optical imaging

Hypoxia alters neuronal function and can lead to neuronal injury or death especially in the central nervous system. But little is known about the effects of hypoxia in neurones of the peripheral nervous system (PNS), which survive longer hypoxic periods. Additionally, people have experienced unpleasant sensations during ischemia which are dedicated to changes in conduction properties or changes in excitability in the PNS. However, the underlying ionic conductances in dorsal root ganglion (DRG) neurones have not been investigated in detail. Therefore we investigated the influence of moderate hypoxia (27.0 ± 1.5 mmHg) on action potentials, excitability and ionic conductances of small neurones in a slice preparation of DRGs of young rats. The neurones responded within a few minutes non-uniformly to moderate hypoxia: changes of excitability could be assigned to decreased outward currents in most of the neurones (77%) whereas a smaller group (23%) displayed increased outward currents in Ringer solution. We were able to attribute most of the reduction in outward-current to a voltage-gated K⁺ current which activated at potentials positive to -50 mV and was sensitive to 50 nM α-dendrotoxin (DTX). Other toxins that inhibit subtypes of voltage gated K⁺ channels, such as margatoxin (MgTX), dendrotoxin-K (DTX-K), r-tityustoxin Kα (TsTX-K) and r-agitoxin (AgTX-2) failed to prevent the hypoxia induced reduction. Therefore we could not assign the hypoxia sensitive K⁺ current to one homomeric K_V channel type in sensory neurones. Functionally this K⁺ current blockade might underlie the increased action potential (AP) duration in these neurones. Altogether these results, might explain the functional impairment of peripheral neurones under moderate hypoxia.     

Effects of transections and electrical coagulations in the medulla oblongata upon the activities in the respiratory muscles of the crucian carp (author's transl)]

The following conclusions may be drawn from the results in this work. The respiratory cycles are formed by the neuronal machinery in the reticular formation under the posterior part of the vagal motor nucleus. The motor neurones or the neuronal networks composing the motor nucleus of the respiratory muscles tonically discharge the action potentials, when the neurones or the networks are released from the inhibitory influences of the interneurones connecting the neuronal machinery to the motor neurones. Furthermore, the interneurones probably generate the tonic discharges after removing the inhibitory influences of the other interneurones or the neuronal machinery on them. A reflex mouth closing is elicited by a mechanical stimulus applying on the upper lip. The motor neurones of the m. adductor mandibulae are activated via only one synapse in the reflex. The reflex action potentials recorded from the motor nerve reduce in amplitude at the resting phase of the nerve in the respiratory cycles. These results suggest that the respiratory motor neurones are by nature spontaneous generators of the tonic action potentials and, in the time of the normal breathing, the tonic activity is interrupted by an inhibitory influence of the neuronal machinery generating the respiratory cycles.     

Time coupling of skeletomotor discharges in response to pseudo-random transsynaptic and transmembrane stimulation

Firing pattern of skeletomotor neurones innervating triceps surae muscles in response to pseudorandom muscle stretching and white noise modulated transmembrane current stimulation was investigated in decerebrate cats. Pseudo-random muscle stretching (upper cut-off frequency 60 Hz, amplitude (standard deviation) ranging from 18.5 m to 40 m) was applied to triceps surae muscles. Membrane potential changes and action potentials of skeletomotor neurones were recorded intracellularly. White noise modulated current was applied through the same (recording) microelectrode. Sequences of ten identical 5 s periods of either muscle stretching or transmembrane current stimulation were applied. Skeletomotor neurones belonging to slow motor units (rheobase less than 8.5 nA) generated action potentials in response to both pseudo-random muscle stretching and transmembrane current stimulation, while firing threshold of those belonging to fast motor units could not be reached by the muscle stretches applied. Peri-spike averaging of muscle length and injected current records showed that the action potentials appeared at the peak of either depolarizing current wave or muscle stretching both preceded by a change in opposite direction (the spikes coinciding with the peak in muscle length PSA being actually elicited by muscle spindle action potentials triggered at the moment of the peak stretching velocity). Time coupling of action potentials occurred during both muscle stretching and transmembrane stimulation, being more tight in the latter case as well as when larger amplitudes of the stimuli were applied. It is supposed that discharges from muscle spindle primary endings phase-locked to small pseudo-random muscle length changes may, due to the time coupling of skeletomotor action potentials, provoke a synchronous firing of skeletomotor neurones, mostly of those belonging to slow motor units. Possible effects of such a firing pattern on the resulting muscle reflex contraction and the stretch reflex stability as well as a possibility of it being provoked by fusimotor discharges are discussed.     

The effect of a vasopressin analog on the reaction of the command neurons in the defensive behavior of the edible snail during nerve stimulation

On the level of snail command neurones of the defensive behaviour an increase was revealed of the amplitude of summary EPSP recorded in command neurones in response to nerve stimulation, an increase of probability of appearance of action potential in the reaction and, under certain conditions, a significant decrease of habituation speed at rhythmic (0.1 Hz) nerve stimulation against the background of peptide. The latter effect was found during comparison of groups of neurones--control neurones and those to which the peptide was presented before the first series of stimulation in the test, i. e. without preliminary elaboration of habituation. The decrease of the speed of habituation concerned both the amplitude of summary EPSP and the probability of action potential appearance in the reaction. All these changes against the background of vasopressin analogue may be the basis of the increase of spike reactions of command neurones of the defensive behaviour and thus the basis of the initiation or the increase of behavioural defensive reactions. The obtained effects were not protracted and took place only in the presence of the peptide in the extracellular medium.     

Effect of disulfiram on the interconnected activity of cortical neurons in trained cats

The action of disulfiram on interconnected activity of neurones in the visual and motor cortical areas was studied in cats with food-procuring conditioned responses to light. Multiunit activity was recorded from the areas and, by means of amplitude discrimination, separated into impulse flows. Crosscorrelation analysis of the impulse series was used to reveal the character and temporal parameters of interconnected activities of neurones firing in correlation within the limits both of the same cortical area and of the two different ones. A depressing action was shown of the disulfiram on the food-procuring reaction, accompanied by a decrease of the number of pairs of neurones from the visual and motor cortical areas mostly acting in interconnection, interactions with long time delays being mostly affected. The character of action of neighbouring neurones in the visual and motor cortical areas changed in the same direction, expressed in their firing by a "common source" type. The question is discussed of disulfiram influence on interneuronal connections of both types suggesting a decrease of alimentary motivation as well as disturbance of food-procuring conditioned motor coordination.     

Dendritic backpropagation and synaptic plasticity in the mormyrid electrosensory lobe

This study is concerned with the origin of backpropagating action potentials in GABAergic, medium ganglionic layer neurones (MG-cells) of the mormyrid electrosensory lobe (ELL). The characteristically broad action potentials of these neurones are required for the expression of spike timing dependent plasticity (STDP) at afferent parallel fibre synapses. It has been suggested that this involves active conductances in MG-cell apical dendrites, which constitute a major component of the ELL molecular layer. Immunohistochemistry showed dense labelling of voltage gated sodium channels (VGSC) throughout the molecular layer, as well as in the ganglionic layer containing MG somata, and in the plexiform and upper granule cell layers of ELL. Potassium channel labelling was sparse, being most abundant in the deep fibre layer and the nucleus of the electrosensory lobe.Intracellular recordings from MG-cells in vitro, made in conjunction with voltage sensitive dye measurements, confirmed that dendritic backpropagation is active over at least the inner half of the molecular layer. Focal TTX applications demonstrated that in most case the origin of the backpropagating action potentials is in the proximal dendrites, whereas the small narrow spikes also seen in these neurones most likely originate in the axon. It had been speculated that the slow time course of membrane repolarisation following the broad action potentials was due to a poor expression of potassium channels in the dendritic compartments, or to their voltage- or calcium-sensitive inactivation. However application of TEA and 4AP confirmed that both A-type and delayed rectifying potassium channels normally contribute to membrane repolarisation following dendritic and axonal spikes. An alternative explanation for the shape of MG action potentials is that they represent the summation of active events occurring more or less synchronously in distal dendrites.Coincidence of backpropagating action potentials with parallel fibre input produces a strong local depolarisation that could be sufficient to cause local secretion of GABA, which might then cause plastic change through an action on presynaptic GABA_B receptors. However, STP depression remained robust in the presence of GABAB receptor antagonists.     

Stereospecific opioid drug receptors on excitable cell membranes

In the past decade evidence has accumulated showing that there are stereospecific opioid drug receptors located on the surface membranes of neurones and skeletal muscle fibres which can block action potentials when opioid drugs are applied to the cells. The nature of this evidence and the difficulties involved in this area of investigation are discussed in detail. Two different mechanisms have been described for this depression of excitability; one, a direct blocking action on sodium channels (or the calcium channels in the case of cells with calcium action potentials) and the other, a stimulation of membrane potassium conductance which results in hyperpolarization and increased membrane conductance both of which decrease excitability. For the most part these different mechanisms seem to prevail in different cell types as will be discussed. Some other points discussed are as follows: first, in higher doses (or concentrations) opioids produce a local anestheticlike effect which cannot be antagonized by opioid antagonists; next, the opioid antagonists which are easily easily available and commonly employed change from antagonists to agonists as their concentration is increased; and finally, the evidence required for the demonstration of stereospecific opioid receptors is considered in some detail.     

Changes in the neuronal reactions of the substantia nigra to nociceptive stimuli during electroacupuncture

The nature of responses of neurones in substance nigra reticular (SNR) part of cats to nociceptive electrical stimulations and change of these responses under the action of electroacupuncture (EA) in the area corresponding to the Tsui-Sang-Li point in man have been studied. The most of the neurons studied (72.1%) responded to nociceptive stimulation either with excitation of inhibition of the impulsive activity. The EA eliminated or changed the effect of nociceptive stimulation in 73.2% of the SNR nociceptive responsive neurones. Intravenous naloxone administration blocked the effect of EA depending on a dose. A conclusion has been made that the SNR neurones are involved in the modulation of nociceptive transmission and that the EA action is directed to some restoration of the nociceptive disturbed balance between the excitatory and inhibitory processes in the SNR neuronal population.     

The analysis of the impulse activity of 2 neurons monosynaptically excitable by a 3rd using cross-correlation histograms and Cox's method. The potential for detecting neuronal and synaptic plasticity

By a method of mathematical modelling exogenic stationary random single impulse activity was reproduced of two neurones (N1 and N2), monosynaptically excited by a third one (N3). Value P12, defined from cross-correlation histogram and Cox coefficient beta 12 were used to evaluate the degree of dependence of N1 and N2 impulse trains. Dynamics of P12, beta 12 and of values of P1*, P2* and P3* proportional to corresponding mean interimpulse intervals of N1, N2 and N3, was studied under changes of efficiency of interneuronal connections, neurones excitability and summate action on them of independent random afferent synaptic inflows. It has been shown that the increase (decrease) of P12 or beta 12 accompanied by decrease (increase) of P1* and P2* is a sign of plastic change or N3 discharges frequency, or a sign of plastic changes of the amplitude of excited postsynaptic potentials elicited by these discharges.     

Synchronization dynamics in the neuronal work of the neocortex and hippocampus during learning before and after the administration of nootropics and narcotics

The basal difference in action of the studied drugs was that nootropics (phenybut in a dose of 40 mg/kg and pyracetam in a dose of 200-400 mg/kg) did not change the initial action of pain reinforcement on synchronism in responses of the cortical neurones of alert nonimmobilized rabbits by inhibitory type (coincidence of the presence and absence of impulse activity) towards its decrease, while narcotics of various types (ethanol in a dose of 4-6 mg/kg, morphine-like opiate DAGO and opioid peptide DADLE in doses of 250 mkg/kg) eliminated the action of pain reinforcement on synchronism in responses of the cortical neurones both by inhibitory and activation (time of coincidence only of the presence of impulse activity) types. These and other drugs mainly weakened the initial action of both the inhibitory and reinforced light flashes of synchronism in neurones activity both by inhibitory and activation types. There was no constant parallelism between changes of synchronization and the frequency of the cortical impulses.     

Elementary transcallosal connections of the rabbit sensomotor cortex]

Antidromic responses of two callosal neurones to a local electrical stimulation of the rabbit sensorimotor cortex may be recorded simultaneously with one microelectrode in the homotopic cortical area. In such recording conditions the relative amplitude of extracellularly recorded action potentials of the two neurones is determined primarily by the distance between these neurones and the electrode's tip. In response to the stimulation of the symmetrical area transcallosal monosynaptic excitation of the callosal neurone may occur; two callosal neurones may exite monosynaptically one and the same recorded neurone. The results suggest the existence of clusters or columns, formed jointly by the bodies and terminals of callosal neurones; a functional interconnection between symmetrical clusters or columns may exist, in particular a positive feedback.     

Effect of vitamin E (alpha-tocopherol) on the spontaneous activity of the cerebral cortex

In experiments on 55 Meriones tamariscinus and 49 white rats the influence of D, L, alpha-tocopherolacetate on background activity of the sensorimotor and visual zones of the cerebral cortex of intact and castrated rodents was studied. Species and sex differences were revealed in animals reaction to vitamin E in doses commensurable with therapeutic ones. It is shown that tocopherol elicits a reduction of frequency and increase of amplitude of ECoGs in Meriones males and female white rats. After animal castration tocopherol action basically changes. It is suggested that the inhibitory effect of vitamin E on bioelectric processes in the cerebral cortex results from a change in the level of free-radical oxidation of lipid components of cellular membranes of cortical neurones due to an intensification of activity of their antioxidant system.     

The characteristics of the neuronal reactions of the cat somatosensory cortex to a heteromodal complex conditioned signal]

On alert cats the change was studied of the activity of the neurones of the sensorimotor cortical area at instrumental reaction to a simultaneous heteromodal complex stimulus. It was shown that in the projection of distal limb areas a group could be singled out of neurones, which changed their activity in one direction depending on the character of presented signals. In these cells an increase of discharges frequency was observed in response to complex stimulus, consisting of light and sound signals. After the extinction of the motor reaction both to the complex stimulus and to its components neuronal reactions of lesser intensity was recorded, what determined the absence of the motor reaction. This group of neurones had receptive fields localized on distal limb areas, it was activated at fulfillment of the movement of catching the reinforcement and belonged to neurones of the pyramidal tract. The neurones with receptive fields on the whole limb surface or changing their activity at the animal pose change, had variable reactions to positive and differentiation stimuli.     

Activity of callosal neurons of the visual cortex in the cat

Activity of 28 identified neurones of the visual cortex was recorded in cats immobilized by d-tubocurarine. Stimulation of the callosal body with a single stimulus or high-frequency train elicited a short-latency antidromic reaction of neurones in the visual cortex whose axons constitute the main part of the large cerebral commissure. Some commissural neurones responded to a single callosal stimulation by two action potentials the first one being antidromic, the second one being of long-latency postsynaptic origin. The second action potential was generated as a result of activation of axonal collaterals of the same neurone or the neighboring callosal neurones. More than a half of callosal neurones responded to a single stimulation of the lateral geniculate body by short-latency antidromic discharges and by long-latency postsynaptic reactions. These data indicate the existence of the systems of two-way neuronal connections, i.e. calloso-geniculate and geniculo-callosal ones.     

Effect of microelectrophoretically applied acetylcholine, noradrenaline, dopamine and serotonin on the discharge of paraventricular oxytocinergic neurones in the rat

The effects of microelectrophoretic applications of neurotransmitter substances and their antagonists on the activity of paraventricular oxytocinergic neurones were studied in urethane anesthetized lactating rats. Oxytocinergic neurones were identified by their antidromic response to the stimulation of the neurohypophysis and by their characteristic high frequency discharge of action potentials approximately 15-20s before reflex milk ejection. Acetylcholine (ACh) excited the majority (75%) of paraventricular oxytocinergic neurones, and none of the cells was inhibited in its activity by ACh. In about half of the oxytocinergic cells, atropine and hexamethonium reduced the number of action potentials during the burst discharge preceding reflex milk ejection. Noradrenaline (NE), dopamine (DA) and serotonin (5-HT) reduced the activity of most (75-100%) of oxytocinergic neurones, and none of the cells was excited by these catecholamines. These results suggest that paraventricular oxytocinergic neurones receive excitatory cholinergic inputs and inhibitory noradrenergic, dopaminergic and serotonergic inputs.     

The frequency dependence of evoked and postsynaptic potentials in the somatosensory cortex of the cat.

Intracellular records were made from neurones of the somatosensory cortex of cats, during stimulation of the ventrobasal complex of the thalamus. The aim of the experiments was to detect correlations between frequency dependence of surface evoked potentials and that of unit discharges. The amplitude of the surface evoked potential showed a strong diminution when the frequency of the thalamic stimulation was raised from 1 cps to 15 cps. In spite of this, frequency dependence in amplitude of unit discharges was never seen. As regards their frequency of occurrence the unit responses (full spikes, dendritic, postsynaptic potentials) behaved differently: a part of them showed increasing, another part gave decreasing occurrence, and the remaining portion did not change it. The authors conclude that temporal dispersion fails to give account for the frequency dependence, therefore further possibilities have to be examined.