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The magnitude of the N1 and P3 waves of event-related potentials (ERPs) recorded in the dog medial frontal cortex were shown to depend on the behavioural context of separate trials. The most prominent P3 waves occurred in two behavioural situations: 1) when an unexpected non-reward followed previously rewarded conditioned responses, and 2) when an absence of the reward resulted in behavioural type shift in the next trial. The enhancement of the P3 seems to be due to a common factor: the discordance between the CR or its results and the previously developed behavioural trend.

Two groups of units with different discharge patterns were identified in dog's frontal cortex during reinforcement period of reversal conditioning. Activity of the first group of units was closely related to reinforcement presentation and was influenced by reward/nonreward history in trials preceding the current one. Units of the second group displayed tonic increase of firing which followed food ingestion and persisted for 4-10 s.

A correlation has been found between the time course of the biological activity of specific oligo- and polypeptide factors in cerebrospinal fluid and the effectiveness of motor function recovery. The fluid as a donor material accelerates the compensatory process in recipient animals with unilateral neocortical damage. The procedure stimulates the formation process of connections of the centrally denervated semisegments of the spinal cord with the somatosensory cortex of the intact brain hemisphere. Endolumbar introduction of cerebrospinal fluid from reconvalescents induced the regress of symptoms of central motor disorders in patients with stroke sequelae.

Unilateral brain damage results in the appearance of oligopeptide factor of complete asymmetry (CAF) producing a lateralized effect on spinal centers during intracisternal administration. The action vector of CAF is determined by the side of brain damage. The right- and left-sided CAF differ in chemical structure. Their CAFs are species-unspecific. The findings suggest that there is a chemical labeling of the right and left brain in the mammals (including man). From this point of view, fundamental and medical aspects of biochemical brain asymmetry are analyzed.

The influence of the donor's cerebrospinal fluid (CSF) on retrograde transport of horseradish peroxidase (HRP) from lumbar cord segments to neurons of the sensomotor cortex (SMC) in rats after the left SMC damage was studied. The CSF of convalescents (21 days after damage) and CSF of normal rats was shown to activate the transport of HRP to neurons of the SMC of undamaged hemisphere in the recipients (second day after damage).

In the paper are summarised the results of investigations of the central mechanisms of reinforcing properties of emotions which have been carried out during the last years in Pavlov Physiological Department of the Institute for Experimental Medicine. An attempt is made to outline a perspective of the future development in this domain of the brain physiology which is a key one for the theory of conditioning.

The authors relate new concepts of the mechanisms of the pathogenesis and compensation of central motor disorders of organic origin, based on experimental exploits of the I.P. Pavlov Physiological Department of the Institute of Experimental Medicine. It is shown that in these mechanisms, of paramount importance is the neurochemical component determining a considerable part of the symptomatology of neurological disorders and process of disturbed functions recovery. Based on the regularities discovered and studies of the properties of the convalescents" CSF, a method of its use has been developed in order to treat residual phenomena after brain stroke or craniocerebral injury. The authors describe the results of the clinical testing of that method, demonstrating its effectiveness in the treatment of chronic neurological patients.

New concepts of the molecular mechanisms implicated in the pathogenesis and compensation of central motor disorders are presented. It has been shown experimentally that specific peptide, postural asymmetry, and inactivation factors, play the leading part in these processes. The detection of these specific factors in the cerebrospinal fluid (CSF) of patients and convalescents allowed one to work out and test clinically a new method of treatment (CSF therapy) of patients with central motor disorders of varying genesis. The results of the clinical observations of two patients' groups (with cerebrovascular brain lesions and multiple sclerosis) are provided.

The structurally specific chemical factors (SSCF) are considered as are differentiation-, regeneration- and normal function-promoting factors of embryonic and adult brain tissue. From this point of view the authors' data concerning SSCF expression after brain lesion are discussed. Analysis is made of the importance of further studies into the identification of these factors and elucidation of the biological role they play in the compensatory processes after brain damage in order to develop new approaches to the treatment of brain diseases.

The effect of the CSF components of the rats who had restored motor deficiency after left unilateral removal of motor neocortex, was studied in the rats with an analogous brain lesion. The first group of animals received a thermostable fraction of the donor CSF containing active factors of the posture asymmetry (FPA). The second group of animals were given a high-molecular fraction of the donor CSF with active factors inactivating the FPA. The first group revealed a significant acceleration of compensatory processes. Only a temporary positive effect was observed in the second group. The findings can be used in neurological clinics when treating motor disorders of central genesis.

Overall 136 patients with cerebral tumors, sequels of craniocerebral injury and brain strokes with motor disorders of varying intensity were examined. Factors of the peptide nature, provoking postural asymmetry of the homolateral hind limb in an experimental animal were detected in the blood and CSF of the overwhelming majority of the patients. Provided the compensatory process runs a favorable course (recovery of motor functions), the neuropeptide factors are inactivated with inactivating substances. The data obtained attest to the advisability of further studies into the activity and nature of the factors of postural asymmetry in patients with cerebral motor disorders with a purpose of elaborating new methods of treatment and rehabilitation.

Experimental findings have shown the significance of the investigation into the problem of memory transfer for the elucidation of mechanisms of conditioning. The existence of a chemical component of these mechanisms was revealed: chemical factors of peptide nature seem to play an important role in the pathogenesis and compensation of neurological disorders following brain lesions, including those occurring during the embryonic period. A new approach to the diagnosis, prognostication and treatment of a number of chronic brain diseases, is suggested. Pathogenetic principles of treatment of some of them are proposed. Some theoretical concepts generalizing experimental findings and clinical observations, are formulated.

By means of the analysis of probabilistic ethological structures of the intraspecies rats behaviour in the test "stranger-resident" and by the method of isolated destruction of the frontal cortex or the left and right hemispheres,--it is established that the frontal cortex of the left hemisphere regulates the intraspecies sociability and keeps it on a certain level, because the change (increase) of the intraspecies sociability is observed only at the unilateral destruction of the left frontal cortex. Isolation from the relatives in early ontogenesis leads to the loss of regulating influence of the left frontal cortex on the intraspecies sociability. In isolated animals the frontal cortex of the left hemisphere regulates the level and probability of the appearance of aggression. The right hemisphere ensures the adequate inclusion of the aggression in the probabilistic ethological structure of the total intraspecies behaviour; at its damage the forms appear of an adequate pathological aggression, and connection is lost between the elements of aggressive behaviour and the acts of intraspecies sociability.

The dynamics of elaboration of simple classical and instrumental conditioned reflexes in snails, rats, cars, dogs and humans was investigated. The dependence between the number of correct responses (in percentages) and the number of reinforcements was significantly approximated with exponential equation including the coefficient describing the initial level of conditioning. Regression analysis gave the opportunity to compare the dynamics of conditioning in different animal species.

The role played by Pavlov's principle of conditioned reflexes in neurosciences is discussed. The problem of interneuronal connections is shown to be key in the system of the sciences. The concept of formation of interneuronal connections underlying the conditioned reflex and long-term memory has been elaborated at the Department of Physiology of the Institute of Experimental Medicine named after Pavlov. Possible mechanisms of associations between the neural memory and cell genome are analysed and the problem of the engram localization and storage are discussed. Special attention is devoted to the role played by the subjective experience, mainly emotions, in the organization of the higher brain functions. The extensive experimental evidence gained by the authors during the recent 10-12 years is generalized.

An attempt was made of a direct transfer to the recipient of postural asymmetry originating after the removal of half of the anterior lobe of the cerebellum in rats. Postural asymmetry of the hind limbs proved to develop in spinal rats after subdural injection of brain extracts of the pathological donors below the spinal section level. Specificity of this asymmetry depending on the side of the cerebellar lesion was shown. The type of the recipient's asymmetry repeated the donor's asymmetry exactly. The brain extracts of control animals produced no asymmetry in the recipients. Additional evidence of the peptide nature of the factor stimulating postural asymmetry development was obtained: pronase inactivated the active brain extract.

It is shown that the process of rat behaviour in probabilistic media ("open field" test) corresponds to the basic conditions which determine the concept of the Markov continuous chain. To characterize the degree of orderliness (non-orderliness) of the integrated behavioural activity, the parameter of the Markov process entropy may be used. Dependence has been found between the level of behaviour entropy and individual characteristics of the organization of orienting-investigating activity of rats in the "open field" test.

The incorporation rate of 3H-leucine into high- and low- molecular weight protein fractions of the motor cortex, hippocampal CA3 field and caudate nucleus was investigated after disruption of nucleus raphe dorsalis and nucleus raphe medialis to show an increase in the incorporation rate. The results obtained are discussed in the aspect of reciprocity of the serotonin- and noradrenergic systems on protein metabolism of the central nervous system.

The cellular process that may be considered as a mechanism of interval-selective functional interrelations between neurons in the mammalian brain identified in the previous studies has been studied in neurons of mollusc Lymnaea stagnalis. This process consists of regular excitability changes resulting in high probability (0.6-1) of the impulse reaction elicited by the subthreshold depolarization current shock applied in time intervals (specific, individual for each neuron) after identical subthreshold conditioned stimulus. It is shown that a cycle of the excitability changes after subthreshold depolarization is not a result of the time summation of electrotonic, local or postsynaptic potentials of a neuron, but may be represented by the endogenous (cytoplasmatic) process insensitive to the mediator application and reversibly changed when one of the modulator peptide (bombesin) is applied.

The possibility of the formation of spinal cord functional asymmetry by the blockade of axonal transport in corticolumbar projections with colchicine was investigated. To identify the blockade of axonal transport, the method of retrograde transport of horseradish peroxidase was used. The blockade of axonal transport led to the formation of the asymmetric functional status of the spinal cord, manifesting in postural asymmetry of the hind limbs and characteristic changes in the pattern of bioelectrical activity of the flexor muscles. An endogenous factor inducing postural asymmetry in intact recipients was detected in the cerebrospinal fluid of colchicine treated animals. Based on the experimental data the conclusion is drawn that interruption of normal axonal transport attests to the destruction of central neurons.

Effect was studied of hemolymph of snails-donors with conditioned food refusal, on learning the same habit by snails-recipients. Facilitation was observed of the recipients' learning depending on the quantity of injected hemolymph and the type of conditioned stimulus. The hemolymph of pseudo-conditioned donors inhibited the learning of intact snails-recipients. The possibility is suggested of appearance in the hemolymph of conditioned snails of one or several chemical factors, capable to facilitate elaboration of the same conditioned reflex.

A model of spinal postural asymmetry produced by unilateral motor cortex destruction was developed. The spinal fixation time of postural asymmetry of cortical origin was determined. CSF way of spreading the factors that induce spinal asymmetry was demonstrated. The factor of spinal asymmetry was shown to be species-nonspecific.

It has been experimentally established that special hypophysiotropic factors--precursors of pose asymmetry factors (PAF) are found in the cerebrospinal fluid of donor animals with cortical lesions during the first postoperative hours. These factors, being specific for the location of the cortical lesion in donor animals, appear to be hypophysiotropic peptide substances inducing the production of corresponding PAF by hypophysial cells. The production of certain PAF by the rat hypophysial tissue cultures under the influence of cerebrospinal fluid from cats gives evidence in favour of species nonspecificity of PAF inductors.

Studies on the effect of chloroquine on frog's rectus abdominis muscle have been performed. Relatively low concentrations of chloroquine, 5 times 10-5 and 2 times 10-4 g/ml inhibited cholinesterase activity and potentiated acetylcholine (ACh)-induced contractions but antagonized carbachol and caffeine contractions, as well as ACh-induced contractions of eserinized muscle. High concentrations (5 times 10-4 and 2 times 10-3 g/ml) non-competitively antagonized contractions to ACh, carbachol, caffeine and potassium. It was suggested that the blocking action of chloroquine was due to its local anaesthetic property and interference with intracellular calcium movements.

In chronic experiments on cats a conditioned reflex to time was elaborated by means of periodic passive liftings of one extremity during continuous subthreshold pressor stimulation of the same limb or during micropolarization of the contralateral sensorimotor cortical with a 0,2--1,8 mca current. In animals conditioned during pressor stimulation, trace motor reactions appeared in response to the stimulation or to micropolarization of the sensorimotor cortex and of several subcortical structures. In animals conditioned during micropolarization, trace motor responses were obtained both to sensorimotor cortex polarization and to pressor stimulation of the "conditioned" leg. The authors suggest a common physiological mechanism of the phenomena observed.

The peptide nature of the posture asymmetry factor (PAF) produced in the brain after unilateral removal of the motor region of the neocortex was established. The inactivation of PAF activity in the brain toward the end of the third week after the removal is due to PAF inactivation by the endogenous factor absent from the intact brain. The molecular weight of the inactivation factor exceeds 5.0 kD that makes it possible to separate it from the PAF by gel filtration on Sephadex G-25. The correlation was marked between the increasing activity of the PAF inactivation factor and the recovery of the initial symmetric functioning of the spinal centers during three weeks after unilateral damage to the CNS.

The increase in the amplitude of the E.C.G. and ventricular contractile force induced by chloroquine sulphate was studied in frogs. It was shown that changes originated in the midbrain and were mediated through the sympathetic nervous system. The transmitter was recognized as a beta-adrenergic agent. The possible mechanism of action of chloroquine on the CNS responsible for the phenomenon observed was discussed.