[The Dual Nature of the Electrical Signals of the Brain (Electrical and Electrochemical) Which Were Recorded With the Help Polarizable Electrodes From Inert Metals].

In the modern neurophysiology opinion was confirmed that the electrical signals of the brain in the frequency band from DC to electroencephalogram recorded with metallic conductors of inert metal implanted in the brain are formed solely by changes in the electric field of the brain. This paper presents a review of the literature and our own data, according to which the formation of these signals involves two factors. One factor is a change in the charge of the electric double layer electrode having a capacitor property and change the value of its charge with changes in the electric field volume conductor--the brain. Another factor is an electrochemical signal is defined by local changes in the redox potential (E) neuronal-glial populations surrounding the electrode. The paper provides an overviews the electrical and electrochemical properties of the electrodes of the inert metals used in electrophysiology. It is shown that each of these factors has the characteristic parameters over time and amplitude. The data of own studies of local changes in E cortex accompanying brain's response to the implantation of electrodes in the brain's cortex, the natural behavior of animals in the wake-sleep, integrative brain function and effect of pharmacological agents. These results give evidence of the highly informative study of local changes in brain E in order to study energy metabolism in the brain of waking animals, and lay the foundation for the study of local changes in brain energy metabolism in free animal behavior.

[Effect of disulfiram on energy metabolism (redox potential shift) coupled to paradoxical sleep episodes in rat cerebral cortex].

Disulfiram (DS) is widely used to treat patients with chronic alcoholism. DS treatment multiplies PS episodes. In this work, DS effect on the number of PS episodes and on the energy metabolism changes in the cerebral cortex (coupled to PS episodes) was investigated for the first time in rats. Polygraphic recording of the redox potential E (with platinum electrodes implanted in several cortical sites), electrocorticogram, neck electromyogram, and general motor activity were made in sleep-wake cycles. Rats received DS (100 mg/kg) with meals for two nights, after which the number of PS episodes increased almost twice during two subsequent sessions (prior to receiving DS). This was evidence of an increase in PS pressure coupled to a decrease of norepinephrine level in the brain. DS also evoked sharp decrease in the amount of the positive E shifts related to PS, which were replaced by the negative E shifts or by the two-phase E shifts (negative-positive waves). The absolute mean amplitude decreased both for the positive E shifts and the negative E shifts. These findings demonstrate prevailing glycolytic compartment as a source of fuel supporting PS and the inhibition in all brain energetic compartments. The data presented well agree with the conception that glycolysis becomes the main source for the brain activity under pathology conditions.

[Weak irregular periodical winces of rats in slow wave sleep (SWS) coupled to the cerebral cortex activation and local falls in the cortex redox potential (E)].

The current study has been fulfilled to advance our pioneer studies of the brain energy metabolism (EM) in animals [Shvets-Teneta-Gurii T. B., 1979: Shvets-Teneta-Gurii T. B., 1986; Shvets-Teneta-Gurii T. B., 1986 et al., 2002]. The gist of this line consists of the simultaneous multipoint measuring local changes in the cerebral cortex redox potential (the E) in animals. Polygraphic recordings of the the E, electrocorticogram (ECoG) and general motor activity were made in sleep-wakefulness cycles of rats. It has been found that transition of rats to slow wave sleep (SWS) was accompanied by the E lowering in the metabolic active sites and by arising compound oscillations in the E. At the same time, irregular periodic weak winces (3-40-sec apart) appeared and were accompanied by the ECoG activation and by the E decrease. There are data that episodes of the ECoG activation in SWS are accompanied by pO2 drops in the brain structures [Sarkisova K. Yu., Kolomeitseva I. A., 1900]. Visual and acoustic stimulation being presented in human slow-wave sleep brings down the brain oxygenation level [Born A. P. et al., 2002; Czisch M. et al., 2002]. In sum, the given facts indicate an increase in the activity of functional units in SWS that are fueled by glycolytic compartment. Recently published data suggest that the astroglia is the major compartment of aerobic glycolysis [Dienel G. A., Cruz N. F., 2006; Magistretti P. J., 2006]. It can be speculated that astroglia plays the especially important part in events taking place during SWS.

Changes in the redox potential of the rabbit cerebral cortex accompanying episodes of ECoG arousal during slow-wave sleep.

The redox potential (E) is a useful measure of the intensity and quality of shifts in energy metabolism. Brain E depends on the ratio of the rates of processes occurred in two compartments of energy metabolism - the glycolysis compartment, in which glucose is split without oxygen, and the oxidative metabolism compartment. The present report describes recording of local changes in E using platinum electrodes implanted into several points in the cortex. In these conditions, decreases in E correspond to local increases in the rates of glycolytic processes in the tissue surrounding the electrode and are related to mitochondrial processes, while increases in E correspond to local acceleration of processes in oxidative metabolism in the tissues around the electrode. Our previous studies in rats showed that during episodes of slow-wave sleep (SWS), metabolically active points of the rat cerebral cortex show significant decreases in E, and it was suggested that these are associated with increases in the rate of glycolysis. At the same time, E showed characteristic oscillations lasting 20-40 sec with amplitudes of tens of millivolts. The experiments reported here demonstrated that slow oscillations in E developing during SWS are created by regular episodes of ECoG arousal occurring during SWS, accompanied by startling of the animal, decreases in E, and inhibition of respiration. We suggest that a homeostasis system operates during SWS to maintain the animal's level of consciousness at a particular level and that this, like any system with feedback, operates in an oscillatory fashion. The role of glycolysis in supplying energy to the cerebral cortex to support the elevated level of consciousness increases.

Local changes in the redox potential in the rabbit cerebral cortex accompanying the acquisition of a conditioned defensive reflex.

The oxidative-reductive (redox) potential (E) of brain tissue depends on the ratio of the speeds of processes occurring in the glycolysis (the evolutionarily ancient energy compartment operating without oxygen) and oxidative metabolism (evolutionarily younger and energetically more efficient) compartments. E in the cortex was recorded using implanted platinum electrodes. A conditioned defensive reflex (CDR) was developed by combination of a light and electrocutaneous stimulation (ECS) of the ear. The results showed that after a series of combinations of the light and the ECS, the light started to elicit a change in E. By 200 combinations, the brain developed both increases and decreases in E during combinations. As the number of combinations increased, increases in E were gradually replaced by decreases. We believe that this dynamic of the balance of the major sources of brain energy supply suggests that formation of the CDR may involve a significant role for subcellular structures receiving energy from oxidative metabolism formed at the relatively young evolutionary level, while the major source of energy for brain function during performance of the acquired CDR is the older evolutionary compartment - glycolysis.

[Local changes in the rabbit brain cortex redox potential accompanying the formation of a conditioned defensive reflex].

The brain E is determined by ratio in rate of processes occuring in two energy compartments--in glycolysis (the more ancient one in evolution) in which glucose is splitted whithout oxygen utilization, and in oxidative metabolism which is younger in evolution than glycolysis and more effective than glycolysis. In the present investigation, the brain cortex E changes were recorded with implanted platinum electrodes. CDR was established by combination of light and electric shock applied to the left ear. It has been found that the combinations started to be accompanied by the E shift after the first 5-20 combinations. The E shifts were widely generalized over the cortex, and both increasing and decreasing E were well expressed within 50-200 combinations. As the number of combination increased, the increases in E were gradually replaced by the decreases in E. This dynamic in the balance of the major sources of the brain energy supply during the formation of CDR demonstrates, in our opinion, that subcellular structures or complexes of cells which appeared at the same stages of evolution as the compartment of oxidative metabolism make a significant contribution to the CDR acquisition when memory traces are created, while brain function during realization of well consolidated CDR are supported mainly by glycolysis.

[Changes in the rabbit brain cortex redox potential accompaning episodes of ECoG-arousal during slow-wave sleep].

Local cortex E variations are well expressive indices of rate and peculiarities of energy metabolism. The brain E is determined by the ratio of processes occurring in two energy compartments in glycolysis, in whish glucose is split without oxygen utilization and in oxidative metabolism. In the present investigation, the brain cortex E changes were recorded with implanted platinum electrodes during slow wave sleep. Under such conditions, the E lowering detects acceleration in glycolytic compartment, whereas the E local rising shows acceleration in oxidative metabolism in the tissue surrounding the electrode. Earlier in rats, we have found that E significantly lowered in metabolic active cortical sites during episodes of SWS, and supposed that acceleration of glycolysis increased. Slow oscillations (a 20-40-sec prolongation of the amplitude up to several dozens millivolts) appeared at the same time. We considered these E slow oscillations to reflect changes in the rate in compartment of glycolysis. In this research, we have found the E slow oscillations to be created by regular episodes of ECoG-arousal which were accompanied by E decreases, i. e. by acceleration in glycolysis. We think the data presented show existence of functional system supporting a low level of arousal. As in any complex system with feed back connections, this system works in oscillatory regime.

Monitoring of the oxidation-reduction state of brain structures in freely moving rats during sleep-waking cycles by potentiometric recording.

Freely mobile mongrel male rats weighing 300-350 g were used for studies of changes in the oxidative-reductive (redox) state of brain tissue during cycles of waking, slow-wave sleep, and paradoxical sleep, by recording the potential of the oxidative-reductive state of brain tissue with platinum electrodes implanted into the cerebral cortex ad hippocampus. Electromyograms were also recorded from the cervical muscles, and overall movement activity was also recorded. A common platinum reference electrode was implanted into the nasal bones. These experiments showed that in rats, episodes of waking and paradoxical sleep occurred on the background of increases in the oxidation-reduction potential state of brain tissue at a series of brain points, which we termed "metabolically active." Transitions from waking and paradoxical sleep to slow-wave sleep were accompanied by decreases in the potential of the redox state. The magnitude of changes in the tissue redox state varied up to 100 mV. It is suggested that transitions from waking and paradoxical sleep to slow-wave sleep are accompanied by dynamic changes in the balance of brain tissue energy metabolism between the main energy sources. Oxidative phosphorylation dominates in waking and paradoxical sleep, while aerobic glycolysis dominates slow-wave sleep. We suggest that this latter should be interpreted as a decrease in the potential of the tissue redox state and the formation within the tissue of oscillations during slow-wave sleep. Formation of oscillations is typical for acceleration of glycolytic processes. Recently published data suggest that the major compartment or aerobic glycolysis is the astroglia.

Dynamics of local changes and oscillations in energy metabolism in the rabbit cerebral cortex during the formation of a conditioned defensive reflex.

Brain energy metabolism associated with different functional states and different types of human and animal activity is accompanied by dynamic changes in the degree of linkage between glycolysis and oxidalive phosphorylation in different cell compartments. These processes are reflected in the redox state of brain tissue and can be recorded potentiometrically as changes in the redox state potential (E) of brain tissue. Studies of E in the cortex of rabbits using implanted platinum electrodes showed that during the acquisition of a conditioned defensive reflex using a combination of a light and a mild electric shock to one of the rabbit's ears, conical E showed oscillations with periods of several seconds after 5-15 combinations. This number of combinations started to be accompanied by generalized changes in E in the cortex, which, at 20-100 combinations, could be either an increase or a decrease in E. As the number of combinations increased, increases in E were gradually replaced by decreases. By 200-400 combinations, occillations in E disappeared and the episodes of decreased E accompanying combinations acquired a stable local character. These results suggest that there is a change in the balance of the major sources of brain tissue energy supply during the formation and stabilization of a conditioned defensive reflex: at the initial stages of acquisition of the conditioned reflex a number of conical points have an energy supply dominated by tissue respiration, while the main energy source for brain function during performance of the acquired conditioned defensive reflex is glycolysis.

[Potentiometric monitoring of the redox state of brain structures of freely-moving rats in sleep-wake cycles]. / Monitoring okislitel'no-vosstanovitel'nogo sostoianiia struktur golovnogo mozga svobodno-podvizhnoi krysy v tsiklakh bodrstvovanie-son putem potentsiometricheskoi registratsii.

Variations of brain tissue redox state potential (E) of freely-moving white rats (300-350 g) in cycles of wakefulness (W), slow-wave sleep (SWS), and paradoxical sleep (PS) were measured by platinum electrodes symmetrically implanted into the frontal and occipital cortices and hippocampus. In addition, EMG of neck muscles and general motor activity of animals were recorded. The common reference electrode was implanted in the nasal bone. It was shown that in some brain sites (called active), episodes of W and PS were accompanied by a rise of E, and during transitions from W and PS to SWS, E dropped. The value of E varied in the range of 100 mV. It is suggested that transitions from W and PS to SWS are accompanied by shifts in the balance between the main energy sources. Oxidative phosphorylation prevails in W and PS, whereas aerobic glycolysis is the main source of energy during SWS. We think that this suggestion is supported both by a decrease in E in SWS and its oscillations typical of glucolytic processes [Aon et al., 1992]. Recent literature data [Bitter et al., 1996] suggest that astroglia is the main compartment for aerobic glycolysis.

Changes in redox potential in rat brain tissue developing during episodes of paradoxical sleep.

Paradoxical sleep is regarded by many authors as consisting of episodes of integrative brain activity, this view being based on data relating to changes in overall brain electrical activity (depression of electrocorticograms or the appearance in electrocorticograms of oscillations at the theta rhythm) and increases in neuron activity, data showing negative changes in the potential of the direct current, and data demonstrating increases in brain temperature and local brain blood flow, increases in glucose utilization, and increases in the levels of free oxygen in brain tissue. We have previously observed that episodes of paradoxical sleep are accompanied by increases in the redox potential of brain tissue (E) by several millivolts. In these experiments, we used a direct current amplifier with a low input resistance (1 Mohm), which decreased the true magnitudes of changes in E accompanying episodes of paradoxical sleep. One of the aims of the present work was to determine more accurate measures of the functional changes of this type of sleep, by using a direct current amplifier with a high input resistance (1 Gohm). The second aim of the present work was to obtain more accurate data on differences in changes in oxidative metabolism in different parts of the brain during episodes of paradoxical sleep, by making simultaneous recordings of E from two points of the brain, using several different combinations of pairs of points.

[Dynamics of local shifts in oscillations and energy metabolism of the rabbit cerebral cortex during formation of a conditioned defensive reflex]. / Dinamika lokal'nykh sdvigov i ostsilliatsii v énergeticheskom metabolizme kory golovnogo mozga krolika v protsesse formirovaniia uslovnogo oboronitel'nogo refleksa.

Brain energy metabolism in different functional states or activities of humans and animals is characterized by dynamic changes in the degree of coupling between glycolysis and tissue respiration in different cell compartments (Fox et al., 1988; Fox, 1989; Pellerin et Magistretti, 1994; Prichard et al., 1991; Schur et al., 1999). These processes determine variations in the brain redox state (Siesjo, 1978) that can be potentiometrically recorded with implanted platinum electrodes as the brain tissue redox state potential E (Puppi et Fely, 1983). This potential was recorded in rat brain cortex with four pairs of platinum electrodes implanted into different symmetrical cortical region (one electrode of a pair being located in the cortical layers, another being located epidurally). In the course of defensive conditioning (after 5-15 combination of a bulb light and a weak electrodermal stimulation of a ear), E oscillations (6-10 per minute) appeared. In this period, stimuli combinations produced the generalized E shifts. Later on (with accumulation of stimuli combinations), the episodes of E increase were replaced by the episodes of E decrease. To the 200-400th combinations, E oscillations disappeared, and E shifts became local and stable. The findings suggest that conditioning shifts the balance between the main energy-producing systems in the brain tissue: at the initial stages of conditioning brain functions are predominantly supported by the energy obtained from tissue respiration, while during the realization of defensive conditioning glycolysis is the main source of energy.

[Oscillations in the oxidation-reduction potential of the brain tissue in rats developing during wakefulness and slow-wave sleep]. / Ostsilliatsii v potentsiale okislitel'no-vosstanovitel'nogo sostoianiia tkani golovnogo mozga krysy, razvivaiushchiesia pri bodrstvovanii i medlennom sne.

Variations of the brain cortex redox state potential (E) were recorded in freely moving white rats (mass of 300-350 g) with implanted platinum electrodes (with the platinum reference electrode in the nasal bone) during sleep-wake cycles. It was found that transitions from the slow-wave sleep to wakefulness were accompanied in the number of cortical areas (metabolic-active sites) by the E rise, while the transitions from the wakefulness to slow-ware sleep were associated with a drop of E. However, the episodes of the short-term arousals during the slow-wave sleep were accompanied by the respective decreases in E thus forming the irregular E variations (1.5-3 min in duration). It was also found that the oscillations of a typical pattern (quasisinusoidal with the frequency of 10-20 osc/min and the amplitudes up to several mV) could take place in the metabolic-active cortical sites. These oscillations were defined as fast E oscillations. During the slow-wave sleep, the less regular oscillations with the lower frequency (1.2-10 osc/min) and higher amplitude were recorded in the same cortical sites. These oscillations were defined as slow. It is suggested that the fast metabolic oscillations of wakefulness are mainly controlled by the mitochondria of neuronal populations, whereas the slow metabolic oscillations which occur in the slow-wave sleep are related with glycolysis in populations of glial cells.

[The modelling of the glycolytic oscillations in the potential of the oxidative-reductive status of the brain tissue in waking and anesthetized rats]. / Modelirovanie glikoliticheskikh ostsilliatsii v potentsiale okislitel'no-vosstanovitel'nogo sostoianiia tkani golovnogo mozga bodrstvuiushchikh i narkotizirovannykh krys.

It was found that chemical hypoxia created by intraperitoneal injection of potassium cyanide (5-7 mg/kg) induced in both waking and anaesthetized (pentobarbital, 40 mg/kg) albino rats a significant decrease in the brain redox state potential (E) monitored with platinum electrodes. This decrease could be accompanied by a generation in some brain points of local chains of gradually damped quasisinusoidal E oscillations. Such oscillations were more expressed in waking than in anaesthetized animals. The frequency range of these oscillations was 4-7 cycles/min. This is the range of overlapping frequency ranges characteristic for the high level of vigilance (5-20 cycles/min) and slow-wave sleep and drowsiness (1.5-6 cycles/min). The amplitude of the observed oscillations was close to the maximal amplitude of the brain E oscillations characteristic for the high level of vigilance (up to several mV). The obtained evidence favors our suggestion that behavior-related E oscillations are formed by the oscillations in the redox balance of glycolysis. The similarity of the normal physiological oscillations and those simulated by us under abnormal conditions suggest a certain common mechanism of their generation.