Conceptual approaches to revealing the function of the structural organization of a neuronal network

Brain is an unexcelled instrument of perception and analysis of intensive information flows and decision making. Joint achievements of neurophysiology and morphology highlight the pathways between neuronal formations of different brain regions and their functions and fine organization of relationships within these formations. However, the principles of information transmission and signal processing in such structures remain hypothetical. The structure of the network executing the function of extrapolation or prediction of input signal values is discussed. Organization of neurons in this network is compared with relationships of neurons in the cerebellar cortex. It is suggested that the considered organization of neuronal relationships and the functions executed by the network are inherent for all brain formations including the brain cortex.     

Analysis of the level of cyclic adenosine-3',5'-monophosphate in structures of the 'informational' and 'motivational' system of the rat brain during active conditioning

The content of cyclic adenosine-3',5'-monophosphate (cAMP) was studied in structures of the "motivational" and "infromational" systems of rat brain after the active avoidance conditioning procedure in rats. Three groups of animals were examined: naive rats, trained (conditioned) rats, and group of the active control presented with uncombined conditioned (light) and unconditioned (electric footshock) stimuli. The content of cAMP was determined in the frontal cortex, hippocampus, amygdala, and hypothalamus of both hemispheres immediately after the retrieval of conditioned reaction one day after conditioning. A significant increase in cAMP level was bilaterally observed in the hypothalamus in the group of active control, and in both hippocampi and the right frontal cortex in the conditioned animals. Positive correlations between the cAMP levels in symmetrical regions of the frontal cortex, amygdala, and hypothalamus were revealed in all the examined groups. Additionally, intra- and interhemispheric correlations were found in the active control and conditioned rats. Patterns of correlation were specific for each of these groups. The observed phenomenon is discussed in term of involvement of "informational" and "motivational" brain structures in the mechanisms of adaptive behavior.     

Neuromediator mechanisms of the effect of the antihistamine agent dimebone on the brain

Dimebone was shown to inhibit monoamine oxidase (MAO) deaminating dopamine and serotonin, decrease dopamine metabolism in the basal ganglia of the rat brain, increase noradrenaline level and depress dopamine deamination in the hypothalamus. Dimebone first increased and then diminished the release of dopamine in the cortex, with the concomitant MAO activation and the increase in dopamine and noradrenaline levels. The in vitro experiments have demonstrated that dimebone (10(-4)) preferentially inhibited MAO activity, type B and dopamine deamination in homogenates of different rat brain structures. The role of MAO inhibition in the mechanism of dimebone action on the catecholamine metabolism in the brain structures and its stimulating effect on CNS are discussed.     

Magnetic resonance image and blood manganese concentration as indices for manganese content in the brain of rats

Neurological disorders similar to parkinsonian syndrome and signal hyperintensity in brain on T₁-weighted magnetic resonance (MR) images have been reported in patients receiving long-term total parenteral nutrition (TPN). These symptoms have been associated with manganese (Mn) depositions in brain. Although alterations of signal intensity on T₁-weighted MR images in brain and of Mn concentration in blood are theoretically considered good indices for estimating Mn deposition in brain, precise correlations between these parameters have not been demonstrated as yet. Male Sprague-Dawley rats received TPN with 10-fold the clinical dose of the trace element preparation (TE-5) for 7 d. At 0, 2, 4, 6, and 8 wk post-TPN, the cortex, striatum, midbrain, and cerebellum were evaluated by MR images, and Mn concentration in blood and Mn content in these brain sites were measured by atomic absorption spectrometry. Immediately after TPN termination, signal hyperintensity in brain sites and elevated Mn content in blood and brain sites were observed. These values recovered at 4 wk post-TPN. A positive correlation was observed between either the signal intensity in certain brain sites or Mn content in blood and the relevant brain sites. Our observations suggest that the Mn concentration in blood and signal intensity in the brain sites on T₁-weighted MR images are reliable indices for monitoring Mn contents in brain.     

Searching activity under different reinforcement regimens and the process of information interaction with the environment]

When training rats in casual environmental conditions the search activity is determined by the regimen of unconditioned confirmation and the probability of a primary chance correct performance of instrumental reactions (PCCR). The value of PCCR determines what part of instrumental reactions will be realized due to a conditioned signal and confirmed appropriately. This, in its turn, influences the informational interaction of the animal with the environment in any regimen of confirmation (constant or probable). With the least favourable values of PCCR for learning a decreased number of confirmation lowers the search activity due to a sharp deterioration of the conditions for acquiring information--both factors (PCCR and low frequency of confirmation) cause single-directed changes (decrease) in informational significance of research reactions. The optimal PCCR values for learning promote informational significance of every search reaction, this leading to, weakening of the relationship between the intensity of the search activity and probability of unconditioned confirmation.     

Long-distance signalling of abscisic acid (ABA): the factors regulating the intensity of the ABA signal

Abscisic acid (ABA) is a stress signal, which moves in the xylem from the roots to the aerial parts of the plant, where it regulates stomatal movement and the activity of shoot meristems. Root growth-promoting microorganisms in the rhizosphere, lateral ABA flows in the root cortex across apoplastic barriers, ABA redistribution in the stem, leaf apoplastic pH values, and the action of beta-glucosidases, both in the apoplast and the cytosol of the mesophyll, play an important role in the regulation of signal intensity. The significance of abscisic acid glucose ester as a long-distance stress signal is discussed.     

Measurement of the blood flow in various areas of the rat brain by means of microspheres]

A method is described to measure regional blood flow in different structures of the rat brain. Microspheres (15 micron) are injected, the brain is sectioned, stained for myeline, radioautographs are prepared and the microspheres in the different structures are counted. The values obtained for different brain structures are counted. The values obtained for different brain regions (cortex, corpus callosum, thalamus hipocampus, hypothalamic region, colliculi, cerebellum, pons, medulla) compare well with those published by others on larger animals. In rats fed 1% of lead from birth, higher blood flow is found in the cortex and a lower one in the interior part of the brain compared to controls.     

A spectral-correlational analysis of the electrical activity of the sensorimotor cortex and the internal geniculate body during a motor-polarization dominant]

By spectral-correlative analysis the dynamics was studied of structural changes of coherent relations of the electrical activity of the sensorimotor cortex and medial geniculate body (MGB) of the rabbit under motor polarization dominant created by the action of DC anode on the sensorimotor cortex area. It was shown, that in the power spectra of the MGB, besides the increase of the delta-region components in interstimulus intervals at the dominant, during the action of the sound stimulus a distinct maximum appeared in the alpha-rhythm range of the electrical activity of MGB of the "dominant" hemisphere. The coherence increase of the delta-range of the MGB and the sensorimotor cortex electrical activity in the "dominant" part of the brain was manifested exclusively in the period of sound stimulus action.     

A comparison of tabun-inhibited rat brain acetylcholinesterase reactivation by three oximes (HI-6, obidoxime, and K048) in vivo detected by biochemical and histochemical techniques

Tabun belongs to the most toxic nerve agents. Its mechanism of action is based on acetylcholinesterase (AChE) inhibition at the peripheral and central nervous systems. Therapeutic countermeasures comprise administration of atropine with cholinesterase reactivators able to reactivate the inhibited enzyme. Reactivation of AChE is determined mostly biochemically without specification of different brain structures. Histochemical determination allows a fine search for different structures but is performed mostly without quantitative evaluation. In rats intoxicated with tabun and treated with a combination of atropine and HI-6, obidoxime, or new oxime K048, AChE activities in different brain structures were determined using biochemical and quantitative histochemical methods. Inhibition of AChE following untreated tabun intoxication was different in the various brain structures, having the highest degree in the frontal cortex and reticular formation and lowest in the basal ganglia and substantia nigra. Treatment resulted in an increase of AChE activity detected by both methods. The highest increase was observed in the frontal cortex. This reactivation was increased in the order HI-6 < K048 < obidoxime; however, this order was not uniform for all brain parts studied. A correlation between AChE activity detected by histochemical and biochemical methods was demonstrated. The results suggest that for the mechanism of action of the nerve agent tabun, reactivation in various parts of the brain is not of the same physiological importance. AChE activity in the pontomedullar area and frontal cortex seems to be the most important for the therapeutic effect of the reactivators. HI-6 was not a good reactivator for the treatment of tabun intoxication.     

Indices of the status of the cholinergic processes in the rat sensorimotor cortex and caudate nucleus at early periods after gamma-irradiation at a dose of 150 Gr

An insignificant increase in the content of acetylcholine-like substances was registered in the rat brain cortex and caudate nucleus 15 min after whole-body gamma-irradiation with a dose of 150 Gy. After 24 h, the number of these substances appreciably decreased. Total acetylcholinesterase activity in the above brain parts gradually decreased throughout the entire period of observation. These indices changed more markedly in the caudate nucleus than in the cortex of the brain.     

A comparison of tabun-inhibited rat brain acetylcholinesterase reactivation by three oximes (HI-6, obidoxime,and K048) in vivo detected by biochemical and histochemical techniques

Tabun belongs to the most toxic nerve agents. Its mechanism of action is based on acetylcholinesterase (AChE) inhibition at the peripheral and central nervous systems. Therapeutic countermeasures comprise administration of atropine with cholinesterase reactivators able to reactivate the inhibited enzyme. Reactivation of AChE is determined mostly biochemically without specification of different brain structures. Histochemical determination allows a fine search for different structures but is performed mostly without quantitative evaluation. In rats intoxicated with tabun and treated with a combination of atropine and HI-6, obidoxime, or new oxime K048, AChE activities in different brain structures were determined using biochemical and quantitative histochemical methods. Inhibition of AChE following untreated tabun intoxication was different in the various brain structures, having the highest degree in the frontal cortex and reticular formation and lowest in the basal ganglia and substantia nigra. Treatment resulted in an increase of AChE activity detected by both methods. The highest increase was observed in the frontal cortex. This reactivation was increased in the order HI-6 < K048 < obidoxime; however, this order was not uniform for all brain parts studied. A correlation between AChE activity detected by histochemical and biochemical methods was demonstrated. The results suggest that for the mechanism of action of the nerve agent tabun, reactivation in various parts of the brain is not of the same physiological importance. AChE activity in the pontomedullar area and frontal cortex seems to be the most important for the therapeutic effect of the reactivators. HI-6 was not a good reactivator for the treatment of tabun intoxication.     

Morphofunctional characteristics of the associative region of the cerebral cortex in experimental neuroses in the dog

Ultrastructure of neurones and synapses of the cortical associative area of dogs has been studied under conditions of experimental neuroses caused by prolonged informational loads with constant time deficit and high motivational signals significance. Analysis of subcellular reorganization of a number of neuronal and synaptic organelles showed the degenerative changes of afferent conducting systems in various neuropil parts leading to the falling out of definite neuronal groups from stable functional connections and to the disturbance of intracortical interrelations. In the cortex simultaneously with destructive processes, are developing intracellular compensatory-adaptive reactions.     

Intercentral relations of the electrical processes of the rabbit brain with a polarization dominant

The dynamics of changes in intercentral relations of electrical activity of the sensorimotor and premotor zones of both hemispheres and the ventroposterolateral (VPL) nucleus of the left and right thalamus at formation of motor dominant under the action of the DC anode in the rabbit sensorimotor cortex was studied by the method of spectral-correlation analysis. It is shown that in the much less than dominant much greater than motor analyzer (the sensorimotor cortex and VPL) highly coherent connections of electrical processes are formed in the delta-range with conjugated lowering of biopotential connections between the structures of the motor analyzer of the much less than nondominant much greater than part of the brain. At the same time differently directed connections of electrical processes are formed between the structures of the motor analyzer, and between the premotor cortex and focus area. Thus, during formation of the much less than polarization much greater than dominant, a new structure of the intercentral relations of electrical processes is established not only in the much less than dominant much greater than but also in the other half of the brain.     

GABA involvement in naloxone induced reversal of respiratory paralysis produced by thiopental

No agent is yet available to reverse respiratory paralysis produced by CNS depressants, such as general anesthetics. In this study naloxone reversed respiratory paralysis induced by thiopental in rats. 25 mg/kg, i.v. thiopental produced anesthesia without altering respiratory rate, increased GABA, decreased glutamate, and had no effect on aspartate or glycine levels compared to controls in rat cortex and brain stem. Pretreatment of rats with thiosemicarbazide for 30 minutes abolished the anesthetic action as well as the respiratory depressant action of thiopental. 50 mg/kg, i.v. thiopental produced respiratory arrest with further increase in GABA and decrease in glutamate again in cortex and brain stem without affecting any of the amino acids studied in four regions of rat brain. Naloxone (2.5 mg/kg, i.v.) reversed respiratory paralysis, glutamate and GABA levels to control values in brain stem and cortex with no changes in caudate or cerebellum. These data suggest naloxone reverses respiratory paralysis produced by thiopental and involves GABA in its action.     

The typological characteristics of higher nervous activity in dogs and the maxima of the cross-correlation function between the electrical activities of the frontal cortex and the brain limbic systems]

Electrical activity of the frontal cortex, dorsal hippocampus, basolateral amygdala and lateral hypothalamus was recorded in eight dogs with chronically implanted electrodes. Mean values of the maxima of crosscorrelation function (MCCF) between electrical potentials in the theta, alpha and beta-2 ranges were used as a basis for assessment of conditions for interaction between these structures. Typological features of the higher nervous activity were assessed by the animal performance under conditions of free choice of the reinforcement mode of a conditioned stimulus: either high probable but of low alimentary quality or with low probability but more valuable. The mean MCCF values in the theta range were higher than in the other ranges. The brain structure which had the high MCCF in the theta-range, at least, with two of the structures under study was considered as "dominant". It was shown that hippocampus was the dominant structure for melancholic dogs, the frontal cortex was in phlegmatics. The hypothalamus was shown to be the "dominant structure" in both sanguine and choleric animals, but, for the most part, its activity was correlated with different structures. Thus, conditions for interaction between the frontal cortex, hippocampus, amygdala and hypothalamus seem to be an important factor, which determines typological features of the higher nervous activity of dogs.     

The neurochemical mechanisms of the formation and consolidation of haloperidol-induced catalepsy

In rat brain cortex, haloperidol initiates the long-term potentiation of K(+)-induced Ca(2+)-dependent noradrenaline (NA) and dopamine (DA) secretion in vitro and in vivo. In both cases, the long-term potentiation is caused by the long-term increase in catecholamine content in the NA and DA terminals, as it has been shown in cortical tangential slices. Acute intraperitoneal haloperidol injection (2.5 mg/kg) evokes catalepsy and increases the content of NA and DA in the brain structures with localization of catecholamine receptors on terminals. This increase appears to be caused, predominantly, by modification of the terminal DA receptors, since only a trend to catecholamine increase is observed in the brain structures with a mixed type of NA and DA receptor localization (on somata and terminals). It is suggested that the long-term and diffuse action of haloperidol after its acute administration consists in the anxiogenic reaction and consolidation of catalepsy without an additional procedure of training and in the absence of unconditioned stimulus.     

The role of phosphorylated glucocorticoid receptor in mitochondrial functions and apoptotic signalling in brain tissue of stressed Wistar rats

Mitochondrial dysfunction is increasingly recognized as a key component in compromised neuroendocrine stress response and, among other etiological causes, it may also involve action of glucocorticoid hormones. In the current study we followed glucocorticoid receptor and identified its mitochondrial phosphoisophorms in hippocampus and prefrontal brain cortex of Wistar male rats subjected to acute, chronic and combined neuroendocrine stresses. In both brain structures chronic social isolation caused marked increase in mitochondrial glucocorticoid receptor that was preferentially phosphorylated at serine 232 compared to serine 246 or serine 171. This increase corresponded with the decreased expression of mitochondrially encoded cytochrome oxidase subunits 1 and 3 in hippocampus, and with their increased expression in prefrontal brain cortex. Prefrontal brain cortex appeared to be more sensitive to chronic stress, since it exibited higher levels of mitochondrial Bax and cytoplasmic Bcl2 compared to hippocampus. Chronic stress also altered the response of both brain structures to subsequent acute stress according to the studied parameters. Therefore, prolonged social isolation may cause susceptibility to mitochondria triggered proapototic signalling, which at least in part may be mediated by the glucocorticoid receptor dependent mechanism.     

Evolution of the regional blood deficit and energy metabolism after induction of transient cerebral ischemia by occlusion of the vertebral and carotid arteries in the rat

A transient brain ischemia of 10 min duration was produced in rats by electrocautery of the vertebral arteries and reversible occlusion of the carotid arteries. Ischemia reduced blood flow to 10-18% of the control values in forebrain structures (cortex, striatum, thalamus) and to 25-50% in the mesencephalon, cerebellum and brain stem. In these last structures, after 30 min of recirculation, the flow rates returned to normal values but a 20-35% reduction of blood flow was present in the forebrain structures, indicating that the development of the postischemic hypoperfusion was related to the severity of the preceding ischemia. After 30 min of recirculation, there was a near complete recovery of the high energy compounds but a residual metabolic dysfunction was evidenced by an increase in lactate/pyruvate ratio and an elevation of the glucose content, suggesting a depression of cerebral metabolism which may account for the brain hypoperfusion.     

Canges in the monoamine content in the cat brain in a unilateral lesion of the cerebral cortex]

A spectrofluorometric study of the changes in serotonin and noradrenalin content was carried out in the cortex of large hemispheres, the hypothalamus and the midbrain on the 5th-6th day after creation of a pathological focus in the area of the occipital portion of the cortex in 12 cats. Diffuse changes in the bioelectrical activity of the brain were revealed on the EEG at this period: there appeared peak-like variations and slow waves of increased amplitude. There was noted a marked decrease in serotonin content in the cortex of the large hemispheres with the prevalance of an effect in the area directly adhering to the focus of affection. A tendency to reduction in serotonin level was revealed in the hypothalamus and the midbrain. The content of noradrenalin in the mentioned structures of the brain showed no significant change. The significance of the serotoninergic structures of the brain in the mechanisms participating in the restoration of the functional condition of the brain after its experimental injury is discussed.     

Influence of neural grafting on rat brain with damaged temporal cortex

This study investigated the feasibility and certain aspects of grafting nerve tissue from 15- and 21-day embryo rats into the left temporal rat cortex damaged by a solution (1 µg/1 µliter) of kainic acid (KA). After unilateral damage induced in the temporal cortex by KA, extensive lesions were found in a number of brain structures (the hippocampus, thalamus, etc.) removed from the KA application site; asymmetry between hemispheres was also revealed from the areas of cross-sections of these structures. In the presence of temporal cortex from 21-day embryos grafted into the lesioned area and setting up axonal connections with the host brain, damage to brain structures removed from the lesioned site was either prevented or substantially reduced. Asymmetry between hemispheres as gauged from the area of their cross sections was no longer present in brain with such grafts; moreover, grafts from 15-day embryos transplanted into a cortex lesioned by KA projected out onto the brain surface, growing and compressing the latter. The damaging action of KA on the host brain extended in the presence of these grafts. A viable graft located within the damaged area is thought to inactivate excitatory transmitters accumulating due to KA action, probably fulfilling the function of the damaged cortex in some measure once connections with the host brain have been set up.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 22, No. 5, pp. 586–595, October–September, 1990.