[Electrophysiological study of the effects of topiramate on neocortical neurons in rats].

The effect of topiramate (topamax) on the electrical activity of frontal cortical neurons of neoencephalon was studied by microelectrode techniques in rats. Topiramate upon acute intraperitoneal administration and microionophoretic application dose-dependently reduced the frequency of spike activity within 17 - 30 min after injection at a dose of 40 and 80 mg/kg. At the same time, the agent did not change the membrane rest potential, and the magnitude and form of action potentials. Microionophoretically applied topiramate decreased the excitatory response to electroosmotically applied ethanol at "small doses" (ejected current < 50 nA) and enhanced the neuronal depression induced by ethanol at "large doses" (ejected current > 50 nA). It is suggested that the attenuation of alcohol seeking behavior observed after topiramate administration is due to suppression of ethanol activating effects in neoencephalon neurons, while the alleviation of alcohol withdrawal is associated with the central depressant activity.

[Glutamatergic excitation of cortical neurons depending on site of origin on the neuronal membrane and cholinergic regulation under hypothermic condition].

In sensorimotor cortical slices of guinea pig in the course of cooling of incubating fluid from 34 to 21-22 delta C it was shown that hypothermia does not influence on the evoked spike reactions to iontophoretic application of glutamate to the soma, but glutamate action on the dendritic locus causes the shot latency somatic spike response during hypothermic increasing of the rate of spontaneous activity and long latency spike response--during hypothermic fall of activity. While the cooling rate of spontaneous activity in the slow firing neurons was mainly increasing and in the high firing neurons (above 4 spikes per second)--decreasing. The changes in spontaneous activity began at 30 degrees C along with the decreased spike reactions to iontophoretic applications of acetylcholine and efficacy of dendro-somatic propagation. At the same temperature the fall of spike amplitude was initiated and increased with further hypothermia. It is proposed that the basis for hypothermic changes of neuronal activity.is the decreased rate of M-cholinergic process at 27-29 degrees C. Neurons of different physiological properties display different sensitivity to hypothermic factor.

[Electrophysiological study of acamprosate effects on frontal cortical neurons in rats].

The effect of drug for alcoholism treatment acamprosate (campral) on spontaneous electrical activity of frontal cortical neurons was studied in rats. Acamprosate after acute intraperitoneal administration (600 mg/kg) and microiontophoretic application reduced the frequency of spike activity in about 30 % of cells studied. The agent didn't change the magnitude and form of action potentials. Microiontophoretically applied acamprosate reduced the excitatory responses to ethanol electroosmotically applied to neurons at "small doses" (ejected current < 50 nA) and increased the value of neuronal depression induced by ethanol at the "large doses" (ejected current 50 nA). Effects of acamprosate were dose independent. It is suggested that acamprosate has no interaction with specific postsynaptic receptors and its action is determined by presynaptic mechanisms.

[Adaptive function of the brain and problems of hypoxia].

Based on the findings of various authors and own experimental data it was concluded that adaptive behaviour is regulated by changing in the level of spontaneous neuronal activity. Spontaneous firing is monitored by brain metabolic M-cholinergic reaction which increased the efficacy of dendritic propagation by mechanism of K+ membrane channels blockade. High energy demands of cholinergic process creates a threat to nerve cells survival in hypoxic conditions.

[Glial satellites as the source of additional energy supply to the neurons during the increased frequency of firing activity].

Using surviving slices of guinea pig somatosensory cortex, it was shown that functionally different regulation of spontaneous firing activity in different neurons corresponded to irregular distribution of glial satellites. Maximal increase of spike activity induced by acetylcholine (up to 36 spikes per second) was detected in "silent" neurons which account for 37.2% of nerve cells in layer V. According to the morphometric analysis, the same relative number of neurons (38.6%) were surrounded with glial satellites. In spontaneously active neurons only a small elevation of firing activity (5-22 spikes per second) above the basal level was recorded. The results allow to suggest that M-cholinergic reaction, controlling the spontaneous activity level, requires the additional energy supply for its maximal expression in inactive neurons. This is achieved by contacts of neurons with the surrounding glial satellites.

[The temperature regulation of the spontaneous activity frequency and the concomitant changes of the cortical neurons' spike amplitude].

In the sensorimotor cortical slices of guinea pigs, the rate of neurons' spike activity increased at 27-29 and 34-36 degrees C. The change of the firing rate was accompanied by a drop in the spike amplitude at the temperature below 27 and above 34 degrees C. Usually after cooling to 24 degrees C the spike amplitude fully restored when the temperature increased to 32-34 degrees C. The fall of spike amplitude at t >35 degrees C could not be stopped by temperatyre decrease. The data obtained indicate the important role of the neuron membrane K+ permeability.

[Spontaneous activity of cortical neurons in vitro and its regulation under the effect of acetylcholine].

In somatosensory cortical slices it was obtained that neuronal firing excitation evoked by iontophoretically applied acetylcholine was depended on the rate of spontaneous activity. The spontaneous firing rate was regulated simultaneously with dendritic properties and expression of cholinergic reaction. All of these findings may be a reflection of changing in K+ membrane permeability.

[Spontaneous activity level and spike responses of cortical neurons to local supply of amino acids for dendrites and soma].

In guinea-pig parietal cortex slices, it was shown that neuronal spontaneous activity depended on dendro-somatic propagation of excitations evoked in dendrites. The functional dendritic properties are essentially non-uniform in the population of cortical neurons. Spike responses to direct soma activations are quite stable among neurons with various levels of spontaneous activity.

[The comparative roles of acetylcholine and noradrenaline in regulation of spontaneous spike activity of cortical neurons].

The effects of acetylcholine and noradrenaline applications on neuronal sponta-neous activity were investigated in slices of guinea-pig parietal cortex. Iontophoretic ejections of both neurotransmitters to the cortical neurons evoked the same-type slowly-developing and long-lasting increase in the rate of spike activity. The different temperature sensitivity of cholinergic and noradrenergic reactions were revealed. During the temperature shift from 32-34 degrees C to 35-36 degrees C the cholinergic effect on neuronal spike activity became extremely strong, that is why even silent at t = 32-32 degrees C neurons became to acetylcholine responsive. Temperature-dependent changes in spike reaction to acetylcholine were accompanied by stable increase in spontaneous spike activity. The noradrenergic reactions did not change with temperature in limits from 32-34 to 35-36 degrees C. In this temperature range spike reactions to glutamate, the main excitation transmitter in the cortex, remained constant. The results obtained suggest that acetylcholine is the main neurotransmitter regulating spontaneous spike activity in cortical neurons.

[Temperature sensitivity of the cholinergic response in cortical neurons of guinea pigs]. / Temperaturnaia chuvstvitel'nost' kholinergicheskoi reaktsii korkovykh neironov kory mozga morskikh svinok.

A temperature change from 20 to 36 degrees C results in a significant increase of neuronal responses to iontophoretic application of acetylcholine in parietal cortex slices. The most intensive changes in cholinergic responses occurred in two temperature zones: 27-29 degrees C and 34-36 degrees C. Increase in the responses to acetylcholine accompany with increasing spontaneous spike activity.

[Cholinergic modulation of neuronal spike reactions to dendritic and somatic application of excitatory acids]. / Kholinergicheskaia moduliatsiia impul'snykh reaktsii neironov na dendritnoe i somaticheskoe podvedenie vozbuzhdaiushchikh aminokislot.

Acetylcholine effects on neuronal firing responses evoked by somatic or dendritic applications of excitatory amino acids were studied in slices of guinea-pig parietal cortex. Excitatory reactions initiated by dendritic activation were enhanced by acetylcholine wherever it was iontophoretically applied: either to soma or dendrites. The effect consisted in shortening spike response latencies and increasing response intensity and duration. The modified responses were recorded within 1-min interval after acetylcholine microinjections at a distance within 300 microns of the soma. Parameters of responses to somatic applications of excitatory amino acids were not significantly changed by acetylcholine. The results suggest that acetylcholine improves dendritic propagation rather than membrane excitability.

[Effect of temperature on impulse activity of cortical neurons in guinea pigs]. / Vliianie temperatury na impul'snuiu aktivnost' korkovykh neironov u morskikh svinok.

The temperature change of incubating fluid from 37 to 24 degrees C results in significant decrease of neuronal spontaneous firing rate in parietal cortex slices. Evoked spike responses to microiontophoretic application of glutamate practically did not change.

[The spike reactions of the motor cortex neurons of old rabbits to specific stimuli]. / Spaikovye reaktsii neironov motornoi oblasti kory starykh krolikov na spetsificheskie razdrazhiteli.

Spike reactions of motor cortex neurons to tactile and electrocutaneous stimulation of a forelimb were studied in aged (6-7-year old) rabbits. As compared with young adult animals, the neuronal reactions to afferent stimuli were rarely recorded in the motor cortex of aged rabbits (66.7 and 50%, respectively). The activation manifested in increasing firing rate over its spontaneous level was less intensive than in young animals. The neuronal reactions of aged animals were characterized by the slower activation with longer latencies and slower development of spike responses. The parameters of slow activation could be partly corrected by the iontophoretic application of acetylcholine to the soma region. Neuronal inhibition recorded in the motor cortex of aged rabbits was not markedly changed compared to inhibition reactions in young animals. It is suggested that impairment of the functional state of dendrites in aging is responsible for the changes observed.

[The reactions of the cortical neurons to the microiontophoretic delivery of acetylcholine to their dendrites]. / Reaktsii neironov kory na mikroionoforeticheskoe podvedenie atsetilkholina k ikh dendritam.

In slices of parietal cortex of a guinea pig spike reactions were studied induced in neurons by iontophoretical applications of acetylcholine to their somata and dendrites. The results were obtained from 128 units. When applied to different sites of the neuronal membrane acetylcholine produced an increase in firing activity nearly in the same percent of cases (50-75%). The reactions to acetylcholine were most typical for spontaneously active neurons. The slow onset (to 8 sec) and long duration (to 25 sec) of responses evoked by acetylcholine point to an involvement of muscarinic receptors. Spike responses evoked by acetylcholine application to soma and dendrites were of the same latencies and magnitude. The most distant dendritic site where the acetylcholine excitation was able to evoke response of the soma was separated from it by 300-400 mcm. It is suggested that acetylcholine excitation propagates from dendritic points to the soma with intracellular biochemical processes.

[The morphofunctional characteristics of the neurons in the sensorimotor cortex of old rabbits during the trace assimilation of rhythm]. / Morfofunktsional'nye kharakteristiki neironov sensomotornoi kory starykh krolikov pri sledovom usvoenii ritma.

Extracellular neuronal activity was recorded from 460 neurons from alert young (5-7 months), middle-aged (54-65 months) and old (66-85 months) rabbits. Trace rhythmic activity of sensorimotor cortical neurons was examined after long-lasting (10-20 min) rhythmic (0.5-2 Hz) electrocutaneous stimulation of the contralateral forelimb. Spectral analysis of spike activity showed age-related differences in capability of producing a rhythm of previous stimulation in spontaneous neuronal activity. In young animals propriate rhythmic fluctuations of firing rate appeared after the first or second sessions of stimulations (on the first experimental day), in middle-aged ones--after 2-4 sessions (on the second or third days); cortical neurons in old rabbits did not exhibit trace rhythmic activity. Significant morphological changes in glial and neuronal cells were observed in sensorimotor cortex of old rabbits. It is proposed that morphological deteriorations may be the reason of the impairement of trace processes during aging.

[Cholinergic sensitivity as an index of the functional differences in cortical neurons in young and old rabbits]. / Kholinochuvstvitel'nost' kak pokazatel' funktsional'nykh razlichii neironov kory molodykh i starykh krolikov.

Acetylcholine-sensitivity of motor cortex neurons was studied in the young and old rabbits. Muscarinic-type excitation in the neurons of old animals was revealed twice less frequently compared to the young ones. The age-related fall in the number of cholinoceptive neurons may be due to general decrease of neuronal activation in the motor cortex during aging. Changes in functional properties of motor cortex neurons with age may have a result that firing rate of movement related neurons becomes insufficient for the effective control of motor function.

[Effect of the microiontophoretic application of acetylcholine on the formation of conditioned reactions in motor cortex neurons]. / Vliianie mikroionoforeticheskogo podvedeniia atsetilkholina na formirovanie uslovnykh reaktsii u neironov motornoi kory.

In alert rabbits the activity of the motor cortex neurones was recorded with simultaneous application of acetylcholine to them in the process of defensive conditioning. Conditioned reorganization, mainly of activation type, were found in 60% of neurones. In most cases conditionally reacting cells were sensitive to acetylcholine. Ionophoretic application of the transmitter promoted the formation of conditioned neuronal responses and increased them in comparison with conditioned reactions evoked in absence of acetylcholine. It is supposed that the influence of acetylcholine on conditioned cellular process is realized due to its action on the state of excitability of the cortical neurones.