Effect of disulfiram on the interconnected activity of cortical neurons in trained cats

The action of disulfiram on interconnected activity of neurones in the visual and motor cortical areas was studied in cats with food-procuring conditioned responses to light. Multiunit activity was recorded from the areas and, by means of amplitude discrimination, separated into impulse flows. Crosscorrelation analysis of the impulse series was used to reveal the character and temporal parameters of interconnected activities of neurones firing in correlation within the limits both of the same cortical area and of the two different ones. A depressing action was shown of the disulfiram on the food-procuring reaction, accompanied by a decrease of the number of pairs of neurones from the visual and motor cortical areas mostly acting in interconnection, interactions with long time delays being mostly affected. The character of action of neighbouring neurones in the visual and motor cortical areas changed in the same direction, expressed in their firing by a "common source" type. The question is discussed of disulfiram influence on interneuronal connections of both types suggesting a decrease of alimentary motivation as well as disturbance of food-procuring conditioned motor coordination.     

Autonomic correlates of the formation of a functional self-stimulation system

Capability of intracerebral electrostimulation to serve as an unconditioned reinforcing stimulus in classical conditioning was studied in rabbits. Changes of such vegetative characteristics as respiration frequency and ECG were taken as criterion of conditioned response (CR) elaboration. In preliminary experiments, optimal parameters of stimulation maintaining the highest level of instrumental self-stimulation behaviour were found for each of the animals. Isolated presentation of the unconditioned reinforcing stimulus led to the increase of respiratory rate. Such kind of stimulation induced tachicardia in 5 animals, bradicardia in 3 ones, and in the remaining 6 rabbits a biphasic reaction was observed with initial tachicardia changing for bradicardia. Reactions were taken as CRs if they were similar to those to the unconditioned stimulus and appeared at the moment of omitted reinforcement. After 10 pairings of conditioned sound stimulus with positive reinforcement, CR changes of the two vegetative parameters were observed in 21,4 per cent of cases. After 40 pairings CRs were observed in 87,5 per cent of trials for cardiac and in 78,5 per cent cases for respiratory components. The results obtained confirm the idea of validity and efficiency of intracerebral stimulation of self-stimulation zones as a factor of positive reinforcement.     

Characteristics of the systemic organization of the cortical neurons in various forms of the manifestation of the conditioned reflex to time

Conditioned food-procuring reflex to time (2 minutes interval) was elaborated in cats. By the method of cross-correlative analysis the combined neurones activity in microareas and between microareas of the motor cortex was compared at various forms of conditioned reflex manifestation. Three types of reactions were considered: A--decrease of respiratory movements amplitude towards the end of the studied interval between reinforcement; B--increase of the amplitude; C--food-procuring paw movement a few seconds before the reinforcement. All three forms of the conditioned reflex to time differed from each other by the level of increase of functional connections number by the moment of the reinforcing stimulus action, and also to a greater extent by the frequency of occurrence of intervals in which the sum of neuronal connections in all simultaneously recorded microareas was greater in the "active" phase than in the "inactive" one. These parameters did not always correlate with the change of impulses frequency of separate neurones which occurred considerably more seldom. All the observed changes were manifest significantly more often when the animals performed the instrumental food-procuring movement than during changes of only the respiratory movements amplitude.     

The indices of rat open-field behavior and the characteristics of the survival and functional recovery of the CNS following circulatory arrest

In experiments on rats it has been shown that for prognostication of successful reanimation after the clinic death of different duration (5, 10, 15 min) correlative interactions between the parameters of behaviour in the open field before blood circulation cessation are more essential than their absolute values. Highly significant correlation coefficients (0.7 and more) between the majority of behaviour parameters were typical for the group of animals which had survived after a prolonged blood circulation cessation (15 min); for rats rehabilitated after 5- and 10-min cessation of the blood circulation--between the characteristics reflecting, basically, the motor-investigating component of the behaviour. In groups of died animals (independently on the duration of clinic death) correlation profile was restricted to characteristics determining only the character of the motor activity. Particular significance is underlined of emotionally psychic components of the behaviour for complete CNS restoration after a prolonged blood circulation cessation in comparison with the shorter ones.     

Stages in the development of neuroses in the dog and effects of preparations with antidepressive and tranquilizing properties

In modelling of neuroses, successive stages of development of this pathology were observed in dogs. The first stage is characterized by circular disturbances of conditioned activity, vegetative shifts of compensatory character and intensification of individual characteristics of behaviour. At the second stage, parallel with sharp disturbances of conditioned reflexes and with vegetative dystonia, a distortion of emotional reactions was observed in dogs. It is essential that resumption of neurotization episodes in experiments on dogs with the second stage of disease promoted a development of depressive-like states. Diazepam corrected the behavioural and vegetative shifts at the first stage of neurosis. Non-typical antidepressants eliminated the manifestation of symptoms complex of the disease, especially at prolonged treatment.     

Effect of destruction of the septum and hippocampus on the shuttle-box avoidance conditioning of the rat

Total destruction of the septum, the dorsal hippocampus (DH), or the lesion of the DH combined with that of the medial septal nucleus in rats was shown to facilitate elaboration of conditioned avoidance responses in a shuttle-box due to an increase of general excitability of the animals, and to cause significant impairment of internal inhibition formation. Lesions of the medial or the lateral septal nuclei as well as a combined lesion of the DH and the lateral septal nucleus had no significant effect on conditioning and internal inhibition elaboration. Therefore the septo-hippocampal connections had different functional directions during active defensive behaviour.     

The relation of the typological classification of dogs to their behavioral characteristics in variations between the probability and the value of reinforcement]

In studying of dogs behaviour in coordinates system "Requirements and probability of their satisfaction" it has been established that selection of behaviour strategy is closely connected with individual typological properties of animals. In experiments with equally-probable alimentary reinforcement a direct correlation was found between the strength parameter of the nervous system and the strategy of dogs behaviour. Animals of strong types manifested the character of reaction which consisted in determination and goal-directedness, while the animals of the weak type manifested other character, having features of uncertainty, indefinition, hesitations. In conditions of conflict between probability and value of reinforcement the dogs manifested two opposite strategies of behaviour: orientation to highly probable events (choleric and phlegmatic) and to low-probable events (sanguinic and melancholic) what is connected with individual properties of functioning and the character of interaction of four brain structures (frontal cortex, hippocampus, hypothalamus, amygdala).     

Cytochemical manifestations of short- and long-term activation of the dopaminergic system of the rat brain]

In order to find correlation between changes in morpho-chemical characteristics of neurons of certain brain structures and changes of the functional state of rats with high horizontal motional activity in "open field" under activation of dopaminergic system caused by short-term and long-term L-DOPA injection aminopeptidase activity and protein content were studied. It was shown that in spite of similar effects of short- and long-term injection on the behaviour of animals, the nature of morpho-chemical changes in the brain differs significantly depending on the duration of the drug injection.     

The characteristics of higher nervous activity and of the brain benzodiazepine system in rats subjected to ethanol exposure in the prenatal period

Exposure to ethanol during pregnancy results in the alternation of 3H-diazepam binding to synaptosomal neocortical membranes from the rat offspring. In male experimental rats, 14 days of age, binding level diminished to 11%. In two-month-old control rats Scatchard plot was biphasic. It has been shown that prenatal exposure to ethanol leads to changes in the nature of binding in two-month-age experimental animals, as compared with the control ones. 3H-diazepam binding changes went along with behavioural deviations. In experimental rats locomotor activity was increased in the "open field" test, passive avoidance conditioned reflex retention was decreased and elaboration parameters of active avoidance conditioned reflex were changed, as compared with the control ones. The data obtained show that higher integrative functions were disturbed by prenatal alcoholization. Correlations between benzodiazepine receptor state and behaviour were studied.     

Features of the formation and dynamics of short-term image memory in the rat

Direct and indirect methods of delayed reactions showed that short-term image memory of rats elaborated on the basis of conditioned signals in poorly developed and its duration is not more than 1 s. While testing this memory, changes in the behaviour were seen, pointing to the development of "hard state" in the higher nervous activity of animals. Short-term image memory based on complex perception was shown to be well developed in rats, and by many characteristics it approximated to the memory of highly organized animals. The ability to reproduce the short-term image memory on the basis of conditioned signals is supposed to be a complex form of psychonervous activity of animals, and in rodents it appears to be at an initial stage of development.     

Temporal organization of interneuronal relations in the cerebral cortex of the cat in relation to the level of alimentary motivation

By means of records of multicellular activity, interneuronal relations and their modifications in two cortical zones (Visual and motor) were studied in cats at different levels of alimentary motivation. For quantitative evaluation of interneuronal relations the statistic method of cross-correlation analysis of impulse trains was used in determining the probability of the appearance of the discharge of one neurone after the impulse of the other one. For groups of neurones in both investigated cortical areas, three-neurones microsystems were singled out and their activity was analyzed by temporal parameters of interaction between neurones at the interval of 120 ms, both within one microarea (intraanalyzer connections) and between microareas of two cortical zones. The correlation of temporal parameters of interneuronal connections (temporal delays in the activity of neuronal pairs) changed depending on spatial localization of neurones and functional condition of the animals. The existence is suggested of "informational" (1-30 ms) and "motivational" (90-120 ms) values of interneuronal relations for interanalyser connections.     

The outlook for the experimental study of the network functions of cortical cells during learning]

The main outcome of the experiments described in the paper is an idea on the gnostic cortical microset. Multineuronal activity recorded from the motor cortex of cats with a conditioned response to time and the following cross-correlation analysis revealed a strict distribution of interneuronal connections within the microsystems (between the adjacent neurons) and variable connections between the remote neurons during the active waiting stage of two minute interval. Additional analysis of the narrow (0.5 ms) peaks of the histograms allowed to form a view on the synaptic interaction in time. It was found that there was different temporal distribution of the spikes in the peak obtained due to correlograms of neuronal pairs. Some cortical neurons demonstrated a visible synaptic activation at the end of the waiting period when other signs of the temporary behaviour were absent. Pharmacological testing functional interneuronal connections with acetylcholine and Ca(2+)-suppressing drug EGTA have raised a question on the neurochemical specificity of the intra- and extracortical synapses.     

Character intercorrelation and the potential role of phenotypic plasticity in orchids: a case study of the epiphyte Liparis resupinata

Character intercorrelation was studied in a natural population of the epiphytic orchid Liparis resupinata in northern Thailand, and patterns of morphological variation in relation to the local growth environment of individual plants were mapped. Massive occurrence of character intercorrelation was detected, but clone size only influenced few characters of individual flowering shoots. Variation in vegetative and floral organs was largely independent, but two cases differed from the general pattern: (1) the only character not defined by size (distance between apices of lateral sepals) exhibited largely independent variation; (2) ovary length was positively correlated with nearly all other characters. Major groups of vegetative and floral characters were found to covary with different combinations of ecological parameters. Although our study does not document the existence of phenotypic plasticity in L. resupinata, the overall patterns observed would be congruent with a scenario involving phenotypic plasticity. No positive correlation between variability and apparent morphological susceptibility to environmental influence was found; but floral characters were generally less variable and covaried with more ecological parameters than vegetative characters. Based on our observations, we make a few methodological recommendations for morphometric studies of species complexes.     

Functional transswitching of dominant motivation in the systems organization of behavioral acts

In experiments on rabbits, instrumental and complex conditioned alimentary behaviour was studied at various ways of raising alimentary motivation to extreme levels. Animals behaviour in these conditions could acquire an outwardly non-motivated (in relation to alimentary need) character. It is suggested that these phenomena are based on the transformation of the dominant motivation and not on the mechanism of "shifted" activity. In experiments on rats, a long "pseudoreinforcement" of extremely enhanced motivation of thirst by ethanol led to profound changes of physiological and neurochemical properties of the primary drinking motivation centres of the hypothalamus. It is suggested that such changes underlie the realization of plasticity properties of the dominant motivation.     

Effect of an analog of vasopressin on the fixation of temporary connections in the intact rat and after destruction of the locus coeruleus

Subcutaneous injection to intact rats and rats with destroyed locus coeruleus of 10 mcg of triglycide-glycinamide-lysinevasopressin (TGDGA-LVP) immediately after elaboration of labyrinth defensive conditioned reflex improves consolidation of temporary connections and raises its resistance to extinction. Improved consolidation of temporary connection is retained in animals with destroyed locus coeruleus for a shorter time than in intact animals. At the same time according to some characteristics, TGDGA-LVP has a more expressed influence of positive character on animals with destroyed locus coeruleus than on intact rats.     

The correlations of the evoked activity of the auditory cortex and amygdala in cats during conditioned reflex activities]

By averaged summary activity of symmetric points of the cat auditory cortex and amygdala evoked by sound, the character of interaction (Spirman coefficient of correlation) was determined between the structures before, at elaboration, at extinction and restoration of instrumental food-procuring reflex and also at automatization of the reflex. Individual character of co-tuning of the cortex and amygdala was found at adaptation of the animal, changing into close interconnections at formation of the reflex and into disturbance of their correlation at its extinction. Stabilization of the reflex up to the stage of automatization was accompanied by the weakening of connections between the cortex and amygdala. The results testify to complex and dynamic character of interaction in the system cortex-amygdala in conditioned activity.     

Effect of a 3-hydroxypyridine-class antioxidant on the functional activity of the central nervous system in mice of different age groups

Characteristics of emotional reactivity, orienting-investigating behaviour and of preservation of conditioned reflex of passive avoidance were used for estimation of the functional activity of animals CNS and also of psychotropic effect of antioxidant 2-ethyl-6-methyl-3-oxypyridine (3-OP) on mice of different age. Studies were carried out on white outbred young (3 months) and elderly (15 months) male mice. Different character was observed of the emotional reactions of different age mice to aversive stimuli and to the open field conditions. Differences were noted of psychotropic effects of 3-OP in 3 and 15-months animals.     

Relation between reactions to pain and the hierarchical rank of animals

Intraspecies experience of domination or subordination in mice is an important factor predetermining their specific behaviour in response to painful stimuli, The significance is emphasized of ethological investigations for studying behavioural reactivity to pain and correct differentiation of responses of "defence-subordination" and "aggression-offence" types. The specificity of diazepam effect on the character of behaviour in response to pain was analysed in animals of different hierarchic rank.     

Disruption of situational reflexes in experimental neurosis brought on by changes in the space factor

Motor activity elaborated in dogs and consisting of delayed choice reactions in a stochastic system (methods developed by Beritashvili, Hunter) and of rhythmic stereotypes of motor situational reflexes (Kupalov method) was not impaired by changes in spatial parameters of unconditioned stimulus in the stochastic system of choosing one feeding trough out of five. The changes in the spatial arrangement of conditioned and unconditioned stimuli in stable stereotypes led to changes in the behaviour of the animals and experimental neurosis with long-lasting disturbances in the situational conditioned reflexes and the short-term memory.     

Identification of brain nuclei implicated in cocaine-primed reinstatement of conditioned place preference: a behaviour dissociable from sensitization

Relapse prevention represents the primary therapeutic challenge in the treatment of drug addiction. As with humans, drug-seeking behaviour can be precipitated in laboratory animals by exposure to a small dose of the drug (prime). The aim of this study was to identify brain nuclei implicated in the cocaine-primed reinstatement of a conditioned place preference (CPP). Thus, a group of mice were conditioned to cocaine, had this place preference extinguished and were then tested for primed reinstatement of the original place preference. There was no correlation between the extent of drug-seeking upon reinstatement and the extent of behavioural sensitization, the extent of original CPP or the extinction profile of mice, suggesting a dissociation of these components of addictive behaviour with a drug-primed reinstatement. Expression of the protein product of the neuronal activity marker c-fos was assessed in a number of brain regions of mice that exhibited reinstatement (R mice) versus those which did not (NR mice). Reinstatement generally conferred greater Fos expression in cortical and limbic structures previously implicated in drug-seeking behaviour, though a number of regions not typically associated with drug-seeking were also activated. In addition, positive correlations were found between neural activation of a number of brain regions and reinstatement behaviour. The most significant result was the activation of the lateral habenula and its positive correlation with reinstatement behaviour. The findings of this study question the relationship between primed reinstatement of a previously extinguished place preference for cocaine and behavioural sensitization. They also implicate activation patterns of discrete brain nuclei as differentiators between reinstating and non-reinstating mice.