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Effects of psycho-emotional stress on contents of steroid hormones in the blood were studied in dogs with different typological properties of the higher nervous activity. Under stress condition, a significant correlation between the cortisol and testosterone levels and the dogs' typological characteristics was found. The more obvious fluctuations in the hormones level occurred in animals with strong and excitable type of the nervous system as compared with dogs belonging to weak and inert type.

This report describes studies of the interaction of the integrative dopaminergic and corticoliberin systems in the neostriatum during performance of situational food-related conditioned reflexes. Studies were performed in dogs with chemotrodes implanted in the substantia nigra and the head of the caudate nucleus. 6-Hydroxydopamine was injected into the substantia nigra at a dose of 50 microg, and 10 microg of corticoliberin was injected into the caudate nucleus. Blood cortisol and catecholamine levels were determined. Analysis of the result showed that an interaction takes place in the neostriatum between the corticoliberin and dopaminergic systems, and that in conditions in which dopaminergic structures are excluded, the efficacy of corticoliberin in the performance of behavioral acts decreases by 30-40%, i.e., complete expression of its regulatory role of motor situational conditioned reflexes is lost.

The paper reviews experimental and clinical data obtained on physiology and pathology of the higher nervous system by the Laboratory founded by I. P. Pavlov during 75 years of its existence: the principle of systemic organisation of the brain structures activity, the role of separate subcortical structures in organisation of behaviour, theoretical development of experimental pathology problems, inner inhibition, the role of sympathetic nervous system in conditioning, possible neurophysiological and neurochemical mechanisms of conditioning.

Interaction between dopaminergic and corticoliberinergic integrative systems in the process of situation alimentary conditioning, was studied in dogs with chemotrodes indwelled in the caudate nucleus head. Following the CRF administration, the cortisol and catecholamine levels were determined in the blood of intact dogs and in the dogs with 6-OHDA impairment of the substantia nigra. The findings suggest that an interaction between the CRF and dopaminergic systems occurs in the neostriatum.

This article presents the results of three series of experiments on cats, dogs, and lower primates, performed to investigate the structural, neurophysiological, and mediator mechanisms of the corticostriatal systems involved in the organization of behavior. Morphological studies of corticostriatal connections showed that along with the diffuse distribution of afferent terminals within the striatum, there were also elements of topical organization defined by anteroposterior and mediolateral gradients. Neurophysiological experiments on dogs and lower primates were used to study the spike activity of the prefrontal region of the cortex and the head of the caudate nucleus during training to conditioned first- and second-order reflexes and during the solution of complex problems involving delayed spatial selection. Studies demonstrated that while in dogs, most of the neurons recorded showed a transition to responses to the conditioned signal at a particular stage of carrying out a conditioned response, in monkeys all cells recorded showed specific responses at different periods of solving the task at all stages of the study. Neuropharmacological experiments on dogs showed that agents blocking glutamine receptors in the caudate nucleus had more pronounced effects at the phase of developing conditioned movement reflexes. Administration of these agents during the reflex reinforcement phase affected only the differentiation of inhibition. These results lead to the conclusion that the prefrontal area of the cortex and, to some extent, the caudate nuclei, act on incoming information specifying the current dominant need and the states of the external and internal environments, to carry out programmed actions and assess the results of these actions.

Experiments in dogs, cats and monkeys revealed that, along with the diffuse principle of afferent terminal arrangement within the striatum, there exist some features of terminal organisation by the anterior-posterior and medio-lateral gradients. The data obtained suggest that the prefrontal cortex and the caudate nucleus head maintain programming of intentions and the evaluation of performed actions.

Experiments in dogs with striatal deficiency revealed an important role of dopaminergic mechanisms in establishment of the situation conditioning. A rearrangement of the background unit activity of the caudate and thalamic nuclei preceding presentation of a conditioned stimulus and correlating with correct accomplishment of a motor task, was revealed in cats. Afferents from intralaminar and ventral nuclei of the thalamus were shown. Participation of striatal, nigral and thalamic levels in systemic organisation of motor conditioning is discussed.

A comparative investigation has been carried out for the first time of the receptor binding of glutamate with synaptic membranes and coarse fractions of the postsynaptic enlargements isolated from the striatum of rats differing in their capacity to develop an alimentary instrumental reflex. It was demonstrated that the number of that glutamate binding sites on the postsynaptic enlargements isolated from the striatum of rats capable of rapidly developing an alimentary instrumental reflex was increased as compared with animals not subjected to training. This relationship is maintained two months after the termination of training.

Situational conditioned reflexes in dogs were studied before and after intracaudate bilateral microinjections of corticoliberin (CRF). Intracaudate microinjections led to an enhancement of locomotor activity, the restoration of earlier extinct exploratory behaviour, impairment of differentiation inhibition, changes of emotional reactions. Behavioural changes were accompanied by shifts of cortisol, vasopressin, norepinephrine and adrenalin levels in blood of experimental animals. The maximal impairment of conditioned behaviour was observed 30 min after CRF microinjections and coincided with maximal activation of pituitary-adrenocortical system. On the basis of the data obtained we conclude that CRF-sensitive systems of the neostriatum participate in the mechanisms, underlying behavioural, vegetative and hormonal changes.

Corticotrophin releasing factor injection into the head of the caudate nucleus of dogs was followed by a more than threefold increase of blood plasma adrenaline and noradrenaline levels as soon as in 30 min and by their reduction by the 60th min after the injection though not to the initial values. These changes are compatible to stressor reaction and are associated with an increased orientation research reaction in animals. Injections of 6-hydroxydopamine into caudate nucleus drastically exhausted dopamine content in this structure. Subsequent injections of corticotrophin releasing factor into caudate nucleus virtually did not change blood plasma catecholamine content, this indicating the participation of the strionigral complex dopaminergic structures in realization of corticotrophin releasing factor effect on the sympathoadrenal system.

The activation was revealed, through a considerable increase of levels of adrenaline, noradrenaline and cortisol. Corticotropin-releasing factor seems to act upon the sympatho-adrenal system (SAS) via dopaminergic mediation. The mechanisms of triggering of the SAS and pituitary-adrenocortical system by the corticotropin-releasing factor seem to be different and due to involvement of different extrahypothalamic structures in the regulating contours.

In this study the results of behavioral, neurophysiological, and morphological investigations in relation to the participation of the corticostriatonigral system in the organization of conditioned reflexes are presented. It was demonstrated in experiments on dogs that blockade of N-methyl-D-aspartate receptors of the caudate nucleus disrupts the realization of consolidated conditioned reflexes and renders their development more difficult. The blockade of quisqualate receptors facilitates the process of differentiation. Switching off of the dopaminergic input makes the development of positive conditioned reflexes more difficult. The reversible switching off of the substantia nigra leads to the reorganization of the neuronal activity of the caudate nucleus in response to the presentation of the conditional signal. Inhibitory nigral influences are directed primarily to the ventromedial divisions of the nucleus, while activating influences are directed to its dorsal segments. The topically organized connections of the motor regions of the cortex with the dorsal region of the caudate nucleus, and of the limbic regions with its ventromedial divisions were studied in morphological investigations on cats. A certain distinctiveness was identified of the spatial organization of the nigrostriatal projections. The data obtained are discussed from the point of view from the systemic organization of behavior.

Within 30-60 min after corticoliberin administration into the dog caudate nucleus, a considerable activation of hypophyseal-adrenocortical system occurred. The motor behavior of the dogs also changed as well as their orienting behaviour, emotional tension, their blood pressure being elevated. Along with its effect on the adrenocortical function, corticoliberin seems to activate behavioural as well as vegetative processes by means of a direct action upon the caudate nucleus' neurons.

Behavioural, neurophysiological and morphological experiments have shown specific influences of cortical and nigral inputs on the neostriatal functioning. The exclusion of cortical inputs resulted in different behavioural effects. Exclusion of nigral, dopaminergic input into the striatum led to impairment of conditioning. The unit activity data have shown that inhibitory nigral influences are mainly directed to the ventro-medial parts of the caudate nucleus, and activating ones--to the dorsal parts of this structure. Morphological studies have revealed topically organised connections of the motor areas of the cortex with dorsal parts of the caudate nucleus and limbic cortical areas with its ventro-medial parts. Some specifics of spatial organisation of nigral projections to the striatum have been shown. Experimental data are discussed in the light of systemic organisation of behaviour.

Neurotic patients with high level of anxiety revealed a specific asymmetry of errors with prevalence of "false anxiety" as expressed by a tendency towards getting ahead of a moving marker on the screen. Reduced efficacy of the operator activity in neurotic patients is regarded as a consequence of a deficiency in the ability to suppress excessive emotional tension induced by involvement in the activity.

New data on the significance of mediator and peptidergic systems of the striatal level in the organization of alimentary conditioned reflexes are presented in this report. The role of acetylcholine-, dopamine-, GABA-and P-ergic systems of the caudate nucleus and the amygdala in the realization of positive and negative conditioned reflexes was investigated. The experiments were carried out on dogs with chemotrodes and microelectrodes implanted in subcortical structures. The results of the experiments with microinjections of the relevant substances into individual subcortical structures showed that activation of the same mediator system in various structures may lead to both unidirectional and multidirectional behavioral effects. On the other hand, the activation of various subcortical mediator systems can lead to identical changes in conditioned reflex activity. The effect of the administration of activators or blockers of a subcortical mediator system depends in many ways on the functional state of the nervous system at the moment of administration and on the localization of the microinjection. It is difficult to predict beforehand the role of various subcortical structures in the organization of integrated behavioral acts. The question of the necessity of studying mediator and peptidergic systems of each subcortical structure in order to understand their significance in the mechanisms of the conditioned reflex is raised.

Bilateral injections of 15 and 45 mcg of synthetic analogue of TYR-D-ALA-LEY-Enkefaline-ARG into the body of the caudate nuclei in dogs produced a manifested increase in parameters of Pavlovian alimentary conditioned reflexes. Moreover, the dose of 15 mcg of LEY-enkefaline enhanced the background salivation and prolonged food consumption. Excited dogs became calm. During analogous injections into the right lateral hypothalamus the effect diminished while injections of 15 mcg of morphine hydrochloride were ineffective. The data point to role of the enkefaline-containing system in alimentary behaviour.

The influence was studied of the near-threshold high- and low-frequency stimulation of the putamen on achievement of alimentary conditioned reflexes in dogs. Both low- and high-frequency activation of the examined structure significantly changes the parameters of intermediate secretion, of the salivary conditioned reflexes, without influencing unconditioned ones. Unilateral stimulation disturbs the achievement of positive and inhibitory conditioned reflexes to a greater extent than bilateral one. Difference between the effects of low- and high-frequency stimulation has been revealed.

The study was carried out on dogs by the secretory-motor method with a two-side reinforcement. Simultaneous and unilateral lesion of the premotor cortex and of the dorsal part of the caudate nucleus head brought about prolonged disturbances of the vegetative components (pulse and respiratory rate) and in the choice of the side of food reinforcement. The change in the magnitude of conditioned salivation, latencies of secretion and motor reaction was temporary, and by the end of the third postoperative period their initial magnitudes were restored. The duration of the disturbances of higher nervous activity depended on the localization and extent of lesion of the caudate nucleus head. Tests were made with chlorpromazine and caffeine before and after the lesion of the brain structures. The tests in the postoperative period revealed latent disturbances in the dog higher nervous activity. It is assumed that the premotor cortex and the dorsal part of the caudate nucleus head are one of the sub-systems involved in the regulation of vegetative, somatic components of unconditioned behaviour and in the analysis of conditioned stimuli.

Neuronal activity of the orbital cortex, the caudate nucleus and the amygdala were studied in chronic experiments on dogs and cats by the method of alimentary and defensive conditioned reflexes. A spatial distribution of neurones involved in the alimentary and defensive conditioned reflexes, was revealed in the caudate nucleus head. The units responding to conditioned alimentary stimuli are localized primarily in the ventral segment. Similarity of responses to surroundings and to trigger conditioned alimentary stimuli was found between the units of the ventral segment in the caudate nucleus head and of the amygdala basolateral part. The influence of stimulation of the amygdala on the orbital cortex units was established in the alimentary conditioned reflex in dogs. A conclusion has been drawn that in elaboration of an alimentary conditioned reflex the neurones of three levels become organized into a definite system, providing for an adequate reaction of the organism to the conditioned stimulus.

In chronic experiments on dogs taught to instrumental avoiding of electrical shock, changes in organization and regulation of movements on electrical stimulation of head of the caudate nucleus via implanted electrodes, were studied. The preliminary low-frequency stimulation increased the latency, altered the posture readjustment, EMGs, and mechanograms of movements. Markedness of the changes depended on the strength of stimulating current. The high-frequency (50 Hz) stimulation either does not affect the response or completely inhibits it. Stimulation against the background of avoiding movements caused its caudal cessation. The quantitative analysis of the movement parameters showed the cessation to be not adequate to analogous cessation of movement under ordinary conditions of cessation of the conditioned stimulus. The data obtained suggest an effect of head of the caudate nucleus on the processes of programming, organization, and regulation of movement.

On the model of biofeedback connection by the given parameters of the EEG alpha-rhythm the dynamics of bioelectrical and vegetative characteristics and correlative connections between them were compared in the pairs of mono- and dizygotic twins. More likeness in the dynamics of the studied parameters was found in the pairs of genetically identical monozygotic twins. There was a maximum increase of the objective similarity characteristics in the moment of activity realization, judging by the change of alpha-rhythm parameters. The obtained results testify to genetic determination of individual specific styles in organization of complex integrative processes of the higher nervous activity.

The characteristics of formation and achievement of motor conditioned reactions were studied in seventeen dogs before and after the lesion of head or body of the caudate nucleus. It has been shown that the degree of higher nervous activity disturbances depends on the localization of injuries in the nucleus, and on the complexity of the tests used. The caudate nucleus exerts a modulating effect on the parameters of motor conditioned reflexes and takes a direct part in the structure of delayed reflexes. Lesion of the caudate nucleus body is attended with more serious disturbances of higher nervous activity than lesion of its head.

In the present paper, human startle reaction (SR) characteristics were estimated by the amplitude of eye-lid reflex and extent of monosynaptic H-reflexes increase. SR depended not only on the parameters of sound stimulation (strength, unexpectedness) but also on the subject's functional state (attention, emotional background). Differences are given of the SR parameters from the orienting reaction. It is supposed that SR is an independent form of emotional-motor reaction of an adaptive character.