[Dependence of "macroscopic fluctuations" from cosmophysical factors. Spatial anisotropy]. / Zavisimost' "makroskpicheskikh fluktuatsii" ot kosmofizicheskikh faktorov. Prostranstvennaia anizotropiia.

It was shown in experiments with collimators that the changes with time in the shape of histograms constructed from the measurements of the alpha-activity of 239Pu microsamples depend on the direction of the flow alpha-particles. If the flow of alpha-particles was directed to the Polar Star, the dependence of the probability of the realization of histograms of similar shape on time disappeared. The measurements of alpha-particle flows directed to the East and West revealed a high probability of the repeated realization of histograms of similar shape in 1436 min, i.e., in a sederal day. A comparison of "west" and "east" histograms showed a high probability of the realization of similar "west" histograms 718 min (half a sideral day) later than "east" histograms. The results suggest that the shape of histograms depends on the pattern of the starry sky and the space-time inhomogeneity corresponding to this pattern.

The paradoxically high reactivity of septal neurons in hibernating ground squirrels to endogenous neuropeptides is lost after chronic deafferentation of the septum from the preopticohypothalamic areas.

The effect of neuropeptides (TSKYR, TSKY and DY) and neurotransmitters (serotonin and noradrenaline) on the activity of medial septum (MS) neurons from the brain of summer wakening ground squirrels (WGS), hibernating ground squirrels (HGS), and hibernating ground squirrels with the undercut septum (UHGS) was studied. It was shown that in HGS, the neuropeptides were substantially more effective in modulating the spontaneous activity of MS neurons than in WGS. The undercutting of MS led to the disappearance of the increased responsiveness to the neuropeptides: in UHGS, neuropeptide-induced changes in the spontaneous activity became nearly identical to those in WGS. The decrease in MS responsiveness in UHGS is due mainly to pacemaker neurons, which cease to respond to the peptides. It was shown that the neuropeptides have a dual effect: they change the level of spontaneous activity through direct modulation of pacemaker potential and control responses to electrical stimulation by modulating the synaptic transmission. Contrary to neuropeptides, neurotransmitters were highly effective in neurons of all groups of animals. Presumably, the enhanced excitability of MS during hibernation, which is necessary for performing the 'sentry post' function, is formed under the influence of the preopticohypothalamic area, and this influence is mediated by peptides.

[Dependence of 'macroscopic fluctuations" on geographic coordinates (from materials of Arctic (2000) and Antarctic (2001) expeditions]. / Zavisimost' "makroskopicheskikh fluktuatsii" ot geograficheskikh koordinat (po materialam Arkticheskoi (2000 g.) i Antarkticheskoi (2001 g.) ékspeditsii).

The detailed structure of histograms constructed from the results of synchronous measurements of the alpha-activity of 239Pu microsamples, conducted in Pushchino (Moscow Region, Russia) and on board the ship "Academician Fedorov" during the Arctic and Antarctic expeditions (2000 and 2001) was analyzed. It was shown that, if the histograms were constructed over a total period of 15 min and more, the "local zone effect" and the circadian periodicity in the similarity of histogram structure, observed during measurements in Pushchino, are not found in measurements on board the ship near the North Pole (latitude 82 degrees). If the histograms were constructed over a total time of 1 min, a strict periodicity ("stellar day" 23 h 56 min) in the appearance of similar histograms in Pushchino and the Arctic and a strict synchronicity of the appearance of similar histograms of measurements in Pushchino and on board the ship at the same local geographical time were observed. During the Antarctic expedition, the effect of synchronicity of the appearance of similar histograms in Pushchino and on board the ship decreased as the ship moved towards the South Pole and the difference in latitude between the points of measurements increased.

[Macroscopic fluctuations: periodicity of the manifestation of "near-zone" effect]. / Makroskopicheskie fluktuatsii: o periodichnosti proiavleniia "éffekta vlizhnei zony".

The "near-zone effect" one of the main manifestations of the phenomenon of macroscopic fluctuations, was further investigated. It was shown that the statistical significance of the near-zone effect varies with time with a period of about 3.5 days. A phenomenological model was proposed to describe the results obtained.

[Forms of histograms constructed from measurements of alpha-decay of 228Ra in Lindau (Germany) and neutron fluxes in Moscow change synchronously according to the local time]. / Forma gistogramm, postroennykh po izmereniiam al'fa-raspada 228Ra v Lindau (Germaniia) i potoka neitronov v Moskve, izmeniaetsia sinkhronno po mestnomu vremeni.

In joint experiments performed at Max Plank Institute of Aeronomy (Germany) and the Institute of Theoretical and Experimental Biophysics in Pushchino, the main manifestations of the phenomenon of macroscopic fluctuations were confirmed. An increased probability of the similarity in synchronous histograms in independent measurements performed by two installations in one laboratory and in two laboratories separated by a distance of 2000 km was shown. In the latter case, the similarity of histograms is most probable at the same local time.

[Correlation of fine structures of distributions of amplitudes of a photomultiplier dark current fluctuations with the Earth rotations about its axis]. / Korreliatsiia tonkoi struktury raspredeleniia amplitud fluktuatsii temnovogo toka fotoumnozhitelei s vrashcheniem Zemli vokrug svoei osi.

The fine structures of distributions of photomultiplier dark current fluctuations measured in two laboratories 2000 km distant from other: in the international Institute of Biophysics (Neuss, Germany) and in the Moscow State University (Moscow, Russia) were compared. It is shown that similar forms of appropriate histograms are apparently more often realized at both locations at the same local time. This confirms the previous conclusion that the fine structure of distributions correlates with rotation of the Earth about its axis.

[Regular changes in histogram forms in physical measurements and mathematical modeling]. / O zakonomernykh izmeneniiakh form gistogramm, poluchennykh pri fizicheskikh izmereniiakh i matematicheskom modelirovanii.

A study of macroscopic fluctuations for objects separated by large distances confirmed the conclusion drawn earlier that, if the objects being measured are in different time zones, the increase in the probability of occurrence of histograms of similar form corresponds to the difference in the local time at the points of measurement. It was also found that, upon realization of pseudo-random sequences of numbers in mathematical generators, sequences of histograms very similar to those in real physical series can be realized. This suggests the presence of previously unknown regularities, both physical and mathematical, in sequences traditionally considered as absolutely random.

[Probability of disturbance of Poisson statistics in radioactive decay type processes]. / O vozmozhnosti narusheniia statistiki Puassona v protsessakh tipa radioaktivnogo raspada.

The phenomenon of regular dynamics of fine structure of sampling distributions in processes of radioactive decay type is discussed. The time dependence of the probability of their similarity indicates that the process measured is nonstationary. The most natural explanation for the disturbance of stationarity is the influence of gauging equipment, which in principle cannot be avoided completely. However, the universality of the effect and the presence of the correlation of the fine structure in independent synchronous processes leads one to suggest the existence of some global source. A mechanism of the generation of fine structure as a result of the influence of nontrivial topology of space on the decay process is proposed.

[Selective cytostatic and cytotoxic effects of avermectins]. / Izbiratel'noe tsitostaticheskoe i tsitotoksicheskoe deistvie avermektinov.

A natural avermectin complex, aversectin C, was shown to be capable of exerting selective cytostatic effect. It killed proliferating neuroblastoma B 103 cells but was non-toxic for differentiated cells of this culture. The activity of aversectin C was related neither to activation of the GABA alpha-receptors nor to their blocking and was at a large extent due to the action of avermectin A1, a component of aversectin C.

The effects of afferent stimulation on neurons in slices of the medial septal area and their modulation by biologically active substances in hibernating and awake ground squirrels.

Evoked neuron activity in slices of the medial septal area and its modulation by neuropeptides and monoamines was studied in two groups of ground squirrels--hibernating and awake animals. Electrical stimulation of the medial forebrain bundle evoked predominantly inhibitory effects of different durations. In addition, responses were seen consisting of resetting of the phase of background volleys to the stimulus after initial inhibition: there were also small numbers of short-latency single-spike responses. All the neuropeptides tested. which had been identified from the brains of hibernating animals, induced differentiated reversible effects consisting of modulation of responses; changes in evoked activity were seen significantly more often than shifts in spontaneous activity. The effects depended on the state of the animal. Thus. peptide TSKYR increased the duration of inhibition in hibernating ground squirrels but shortened inhibition in awake animals. Peptide TSKY. which had little effect in hibernating animals, increased the duration of inhibition in awake animals. Dipeptide DY. which decreased the duration of inhibition and increased the amplitude of the activatory components of responses in hibernating ground squirrels. had little effect in awake animals. The effects of noradrenaline and serotonin correlated to a large extent with their effects on spontaneous activity. It is suggested that endogenous substances are involved in creating the conditions required for increasing the latent excitability and reactivity of septal neurons during hibernation. This allows the medial septal area to function as a "sentry post," allowing the receipt of signals and urgent arousal during hibernation.

[Effects of the afferent stimulation on neurons in the medial septal region slices and their modulation by biologically active compounds in hibernating and waking ground squirrels]. / Vliianiia afferentnoi stimuliatsii na neirony v srezakh medial'noi septal'noi oblasti i ikh moduliatsiia biologicheski aktivnymi veshchestvami u giberniruiushchikh i bodrstvuiushchikh suslikov.

Responses of the medial septal (MS-DB) neurons to electrical stimulation of the medial forebrain bundle (MFB) and their modulation by some neuropeptides and monoamines were investigated in brain slices taken from two groups of ground squirrels-hibernating (HGS) and waking (WGS). Electrical stimulation evoked mostly inhibitory effects of various duration. Besides, responses by phase reset of the background rhythmic bursts and short-latency single spike responses were observed. The neuropeptides identified in the brain of hibernators differentially and reversibly modulated responses even in those neurons where they did not influence the level and pattern of the background activity. Effects of the peptides were state-dependent. E.g., the peptide TSKYR increased the duration of inhibitory effects in the HGS but shortened them in the WGS, while TSKY which had low efficacy in the HGS, increased the duration of inhibition in the WGS. Dipeptide DY depressed inhibitory components and augmented excitatory components of responses in the HGS but was much less effective in the WGS. Effects of noradrenaline and serotonin had stronger correlation with their influence on spontaneous activity. It is suggested that endogenous substances provide for the increased latent excitability and reactivity of the MS-DB neurons during seasonal hibernation. Thus, the MS-DB may function as a "sentry post" participating in signal detection and urgent arousal during hibernation.

[The state-dependent action of neuropeptides and monoamines on the background neuronal activity of the medial septal area in hibernating animals]. / Zavisiashchee ot sostoianiia deistvie neiropeptidov i monoaminov na fonovuiu aktivnost' neironov medial'noi septal'noi oblasti u gibernantov.

Neuronal activity of the medial septal area (MS-DB) was recorded extracellularly in brain slices from two groups of Yakutian ground squirrels Citellus undulatus--hibernating (winter period) and actively waking (summer period). Effects of three neuropeptides identified in the brain of hibernators (TSKYR, TSKY, and DY) and of two monoamines (serotonin and noradrenaline) on spontaneous activity were analyzed. All neuropeptides reversibly changed the levels of the background activity, but in the hibernating ground squirrels (HGS) the level of reactivity (47-56%) was significantly higher than in the waking ground squirrels (WGS, 25-30%). Serotonin also showed some tendency to higher efficacy in the HGS. Only noradrenaline was equally effective and had absolutely dominating excitatory effect in both states, although the level of excitation in the HGS was higher. All other substances evoked excitatory and inhibitory effects in various proportions. Their distribution was state-dependent, the rate of development, intensity and duration of the effects were greater in the HGS. The experiments confirmed the data on higher excitability and reactivity of the septal neurons in the state of hibernation. It is suggested that the tested neuropeptides may participate in the control of hibernation.

State-dependent effects of some neuropeptides and neurotransmitters on neuronal activity of the medial septal area in brain slices of the ground squirrel, Citellus undulatus.

Neuronal activity of the medial septal area was recorded extracellularly in brain slices taken from hibernating (winter) and waking (summer) ground squirrels. The effects of neuropeptides identified in the brain tissue of hibernators (Thr-Ser-Lys-Tyr, Thr-Ser-Lys-Tyr-Arg and Asp-Tyr) on the background activity and responses to electrical stimulation of the median forebrain bundle were analysed. For comparison, the effects of bath application of noradrenaline and serotonin were also tested. Spontaneous activity in half of all neurons (47-56%) was changed under the influence of neuropeptides in hibernating ground squirrels, while in waking ground squirrels the proportion of responsive neurons was significantly lower (25-30%). The tendency for higher efficacy in hibernating ground squirrels was observed for serotonin; only noradrenaline was equally effective in both groups of animals. Electrically evoked responses of the medial septal nucleus-nucleus of the diagonal band neurons were also strongly modulated by neuropeptides; their changes could occur in the absence of shifts in the level and pattern of spontaneous activity. All three neuropeptides had differential action on the level of spontaneous activity, as well as on inhibitory and excitatory components of electrically evoked responses. Thus, the character and distribution of the effects were state dependent and differed greatly in hibernating and waking ground squirrels. The experiments confirmed that medial septal nucleus-nucleus of the diagonal band neurons have higher excitability and responsiveness to some neuropeptides and neurotransmitters in hibernating ground squirrels.The data obtained suggest an increased latent excitability and responsiveness of septal neurons during hibernation and their possible active participation in urgent arousal under the influence of sensory signals.

Background activity of rabbit hippocampal neurons in conditions of functional exclusion of structures which regulate the theta rhythm.

The functional importance of theta modulation in the activity of hippocampal neurons was further analyzed using a method consisting of controlled sequential short-term (25-30 min) inclusion or exclusion of the theta rhythm by local administration of lidocaine into the median cervical nucleus and medial septal region respectively. Studies were carried out using conscious rabbits with extracellular recording of hippocampal neuron activity in field CA1. Administration of lidocaine into the medial septal nucleus and diagonal tract nucleus (MS-DT) led to complete inhibition of theta modulation in neuronal and total hippocampus activity. The mean frequency of background discharges underwent no change in most neurons, but decreased significantly in a limited group of cells with high-frequency activity (presumptive inhibitory neurons). Administration of lidocaine into the median cervical nucleus (MCN), the source of serotoninergic pathways to the MS-DT and hippocampus, was accompanied by increases in the stability and frequency of theta modulation of neuronal activity, induction of theta modulation in an additional group of neurons, and expression of a continuous theta rhythm in the electrical activity (EA) of the hippocampus. The mean frequency and regularity of discharges increased in most cells. These data support the existence of tonic inhibitory effects on the part of the MCN on the septa-hippocampal system generating the theta rhythm; in this regard, the MCN can be regarded as an antagonist of the activating reticular formation.

Spontaneous activity and sensory responses of hippocampal neurons during persistent theta-rhythm evoked by median raphe nucleus blockade in rabbit.

Spontaneous activity and responses to sensory stimuli were analysed in the hippocampal CA1 neurons of chronic unanesthetized rabbits before and after reversible functional blockade of the median raphe nucleus and medial septal area by local microinjections of anesthetic lidocaine. This evoked, correspondingly, persistent theta rhythm and its complete blockade for about 30 min. The results were compared to the neuronal data obtained earlier in the experiments with cholinergic drugs modulating expression of theta rhythm. Intra-median raphe nucleus injection of lidocaine evoked uniform increase of discharge rate in the hippocampal neurons with low and high spontaneous activity. Theta modulation of neuronal activity had increased regularity and frequency (by 0.5-2.0 Hz) and appeared in additional group of the neurons simultaneously with expression of persistent theta in the hippocampal electroencephalogram. Sensory responsiveness of the hippocampal neurons was drastically decreased (45% of the responses preserved). Reactions of all types were blocked, diminished, or inverted, but inhibitory responses were the most severely affected. Injection of lidocaine into medial septal area also blocked all brain stem afferents ascending to the hippocampus via medial septal area, thus, totally depriving hippocampus of brainstem-septal input. However, besides the total absence of theta modulation, spontaneous activity in majority of neurons was not significantly changed. Responsiveness to sensory stimuli also remained relatively high (77% of the responses preserved); on-effects were especially resistant to medial septal area blockade. Comparison of spontaneous and evoked activity in two theta states (physostigmine and median raphe nucleus blockade) revealed striking similarity of all characteristics, which suggested that theta-suppressing influences of median raphe nucleus (presumably serotonergic) are realized primarily through the control of cholinergic septo-hippocampal theta-generating mechanism. However, as the frequency of theta rhythm does not depend on it, an additional effect of disinhibition of activating reticular formation by the median raphe nucleus suppression is suggested. The data confirm that theta rhythm may be regarded as active filter in the information processing by the hippocampal neurons.

Selective cytostatic and neurotoxic effects of avermectins and activation of the GABAalpha receptors.

A natural avermectin complex, aversectin C, was shown to be capable of exerting selective cytostatic and neurotoxic effects on mammalian cells. Specifically, it killed proliferating neuroblastoma B103 cells but was non-toxic for differentiated cells of this culture. The antiproliferation action of aversectin C was not inhibited by bicuculline or picrotoxin, antagonists of the GABAalpha receptors, and was partly due to the action of avermectin A1, a component of aversectin C. Aversectin C irreversibly suppressed activity of 60% neurons in medial septal slices of the rat brain. More than 55% of them were the GABAalpha- and B1-sensitive neurons whereas the rest, about 45% neurons, were the GABAalpha-insensitive and the neurotoxic effect of aversectin C was caused mainly by the B2 component.

[The neuronal background activity of the rabbit hippocampus during functional exclusion of the structures that regulate theta rhythm]. / Fonovaia aktivnost' neironov gippokampa krolika pri funktsional'nom vykliuchenii struktur, reguliruiushchikh teta-ritm.

A method of controlled successive short-term (25-30 min) stabilization or suppression of the theta rhythm by local injections of lidocaine into median raphe nucleus or medical septal area (MS-DB) was tested for further analysis of the functional significance of theta-modulation in activity of hippocampal neurons. Extracellular recording of their activity (area CAl) was performed in unanaesthetized rabbits. Injection of lidocaine into MS-DS resulted in total suppression of theta modulation in neuronal activity and EEG of the hippocampus. Mean frequency of the background activity was not changed in the majority of the units but was significantly increased in a limited group of high-frequency neurons (putative inhibitory cells). Injection into medial raphe, the source of serotonergic afferents to MS-DB and hippocampus, was followed by an increase in regularity and frequency of theta modulation, by appearance of additional group of neurons with rhythmic modulation, and by expression of continuous theta in the hippocampal EEG. Mean frequency of discharge and its regularity were significantly increased in the majority of the cells. The data confirm the presence of tonic inhibitory control of theta-generating septo-hippocampal system by the medial raphe nucleus, which can be regarded as an antagonist of the midbrain reticular formation in this respect.

The effect of some peptides from the hibernating brain on Ca2+ current in cardiac cells and on the activity of septal neurons.

The effects of the peptides TSKYR and DY isolated from the brain of hibernating ground squirrels on Ca2+ current were studied. TSKYR activated Ca2+ current in frog auricle fibers and in single cells from frog ventricle whereas DY blocked Ca2+ current in both preparations. In isolated rat and ground squirrel cardiocytes, TSKYR had no effect on Ca2+ current, and DY increased it. In brain slices of rat, DY blocked the activity of medial septal neurons. TSKYR increased activity of septal neurons at the initial phase, which was followed by decrease of neuronal activity.

[The comparative characteristics of the neuronal activity in surviving slices of transplanted and intact neocortex]. / Sravnitel'nye kharakteristiki aktivnosti neironov v perezhivaiushchikh srezakh transplantirovannogo i intaktnogo neokorteksa.

The background single unit activity and single or multiunit responses to electrical stimulation of the rat's embryonic cortex, grafted into the somatosensory cortex of adult rats were investigated in a slice preparation. The same characteristics of the intact cortex neurons were observed as a control. The percentage of neurons with background activity within grafts was higher, than that within intact neocortex slices (23% and 6%, respectively). However the percentage of neurons responding to electrical stimulation of the recipient neocortex was lower in grafts. The mean latency of multiunit responses of graft neurons was longer, than that of neurons of the intact neocortex recorded at the same distance from the stimulating electrode (19.4 +/- 5.0 and 5.8 +/- 1.1 ms, respectively). Duration of the evoked population discharges was approximately ten times longer in grafts. It is concluded that there are local functional connections between a graft and the host brain and that inhibitory processes within grafts are weak. Functional integration of grafts with the host brain of the recipients after cranial trauma is shown.