Effect of a cyclic enkephalin analog on the protein content in the hippocampal neurons of rats during the acquisition of a 2-way avoidance conditioned reflex

The protein content has been determined by means of cytointerferometry in neurons of fields CA-1 and CA-3 of the dorsal hippocampus in rats, which were trained in a conditioned reflex of two-way avoidance (CRTA) with the action of subcutaneously injected enkephalin cyclic analogue (ECA) in a dose 10 mkg. It has been found that after ECA injection the protein content in the neuronal nuclei of the hippocampal CA-3 field reduces. The acceleration of the CRTA elaboration occurring during the action of ECA is accompanied by a drastic increase of the protein content in the neuronal nuclei of the CA-3 field. The ECA administration to the rats of the active control groups to which were presented the same number of unpaired conditioned and unconditioned stimuli as during the CRTA elaboration also enhances the protein content in the neurons of the CA-3 field. The rats of all investigated groups in the neurons of the CA-1 field display no such significant shifts. The conclusion has been drawn that ECA produces a regulating influence on protein metabolism in hippocampal neurons depending on their functional state.     

Changes in the frequency of the hippocampal theta-rhythm in the dog exposed to a conditioned food stimulus

Frequency changes of hippocampal theta-rhythm in the process of elaboration of coinciding or delayed instrumental alimentary reflex was studied in two dogs. Determination of dominating frequency of rhythmical activity was carried out by means of mathematical methods of analysis on a computer. It was found out, that during the action of conditioned alimentary stimulus the frequency of dominating oscillations became enhanced. Animals with a more frequent initial theta-rhythm formed the delayed alimentary reflex more rapidly.     

Emotional stress during conditioned reflex transformation of heterogeneous instrumental reflexes

The factors leading to pronounced emotional stress accompanied by changes in electrical activity of hippocampus were studied in four dogs during elaboration of conditioned switching-over of heterogeneous instrumental reflexes. Objectively recorded signs of emotional stress were observed in two cases: when the animal was not accurate enough in discerning defensive and alimentary situations and throughout the improvement of instrumental defensive reflex. Pronouncement of hippocampal theta-rhythm increased at those stages of switching-over elaboration where the probability of successful avoiding pain stimulation was relatively low. The data obtained permit the conclussion that theta-rhythm is the correlate of the degree of the emotional stress and not only a manifestation of general arousal reaction depending on the level of sensory input.     

Changes in the electrical activity of the hippocampus during elaboration of an inhibitory reaction in the dog

A conditioned alimentary instrumental reflex was elaborated in three dogs with chronically implanted electrodes to a consecutive complex conditioned stimulus consisting of two equal acoustic stimuli separated by a pause. At first, the animals reacted with motor reactions during the whole action of the complex signal. Then inhibition of reaction was elaborated at first in pause and then in response to the preparatory stimulus. In the process of stabilization of inhibition, there was an increase of similarity of spectral composition of hippocampal theta-rhythm with the values obtained in the inter-signal period. Conclusion is made that the hippocampus is not a structure necessary for the elaboration of internal inhibition. The frequency of hippocampal theta-rhythm may serve as a characteristic of the property called in Pavlov's school mobility of the nervous system.     

Intralimbic evoked potentials in the formation of an instrumental food conditioned reflex to hippocampal electrostimulation in dogs]

In dogs with the electrodes implanted in the hippocampus, amygdala, septum and hypothalamus an instrumental alimentary conditioned reflex (CR) was elaborated to electrostimulation of the hippocampus. Intralimbic evoked potentials (EPs) were studied during the elaboration and extinction of this reflex and during stimulations of limbic structures conducted with the purpose of CR generalization checking. Late EP components in the lateral hypothalamus and central nucleus of the amygdala changed during CR elaboration and extinction and in the hippocampus during amygdala testing. In both cases the amplitude of trace positivity and of slow negative wave was less, when during stimulation of the structure an instrumental movement was initiated than at its absence.     

Effect of electrocoagulation of the septum on the behavior and memory of the cat

Lesion effects of various areas of the septum on general behaviour, learning and memory were studied in cats. It appeared that electrocoagulation of the medial septum alone leading to the disappearance of the hippocampal theta rhythm does not result in the development of the septal syndrome signs; does not disturb the normal structure of the sleep-wakefulness cycle; does not delay the elaboration of instrumental alimentary reflexes (to approach two feeders) or their extinction, but does entirely disturb the delayed responses to conditioned stimuli. In cases when lesion involves also the lateral septum, it produces the development of all signs of the septal syndrome (hyperemotionality, hyperactivity, rage, hyperphagia, etc.), disturbance of the normal structure of the sleep-wakefulness cycle, delay of both the elaboration and extinction of instrumental alimentary reflexes, disturbance of pre-elaborated conditioned reactions with sound discrimination, entire disturbance of conditioned delayed responses. On the basis of these data, the specific significance of hippocampal theta-rhythm in the organization of learning and memory is rejected, and a more important role is attributed to the descending regulatory influence exerted by the hippocampus and other archipaleocortical structures on the activating and motivatiogenic structures of mesodiencephalon.     

Effect of neurotizing exposures on conditioned reflex activity in the late postresuscitation period in rats

In white rats resuscitated after 10-minutes stop of the blood circulation, conditioned switching over was elaborated on the basis of alimentary and defensive instrumental reflexes and the effect was studied of neurotizing influences. Single application of electrocutaneous pain stimulus in alimentary situation ("collision") led to more expressed disturbances of conditioned activity in resuscitated rats than in intact ones. Differentiation of a signal different from the positive conditioned stimulus only by the height of the tone, was practically not elaborated in resuscitated rats, and the disturbance of the conditioned alimentary reflex to the reinforced signal appearing during differentiation elaboration, was manifest in them to a greater degree. The obtained data testify that even a short-time brain ischemia, accompanied by a fast and full restoration of the neurological status, leads to functional defects of the CNS appearing at subsequent neurotic influences.     

Functional organization of limbic brain structures during conditioned reflex activity in the dog

In experiments on 3 dogs it was shown that instrumental defensive conditioned reflex (CR) to electrical stimulation of the hippocampus is generalized within the limbic system (LS). The rate of generalization depended on the place of testing stimuli in LS. Stimulation of the medial parts of LS at the stage of stabilized initial reflex did not produce the generalized CRs, while they appeared distinctly in response to stimulation of the lateral parts of LS. In the process of elaboration of heterogeneous CRs (defensive and alimentary) to electrical stimulation of the hippocampus, generalized conditioned reactions from some brain structures appeared in both situations to the same degree while from other structures--with considerable differences. These data point to a possible participation in the genesis of the generalized CRs both of signal and reinforcing brain mechanisms.     

Integrative properties of parietal cortex neurons of rabbits during the switching of heterogeneous classical conditioned reflexes

The impulsive activity of parietal cortex neurons of rabbits during the elaboration and specialisation of switching-over of alimentary and defensive conditioned reflexes has been studied. There are changes of parietal cortex neurons activity correlated with the stages of switching-over elaboration. The significant differences of the background neurons activity and neurons response to the conditional signal during alimentary and defensive conditioned reflexes have been established. The dominant motivation influences the neurons activity by modulation of background and conditioned activity of neurons. The integrative properties of neurons investigated in switching-over situation are revealed in their ability to summarize the excitation coming to the same sensory input with excitation from different motivational and reinforcement systems.     

The possibility of elaborating conditioned reflexes on the basis of emotional reactions evoked by electrical stimulation of limbic structures]

In experiments on cats with chronically implanted electrodes a conditioned stimulus (200 c/s tone) was paired with electrical stimulation of limbic structures, which produces pronounced emotional behaviour: defensive, aggressive, alimentary or drinking reactions. It has been shown that conditioned reactions are not elaborated on the basis of electrical stimulation, which activates alimentary, drinking or aggressive behaviour. Neither is a conditioned reflex formed to the combination of sound and stimulation of the brain structures, which inhibits alimentary behaviour. A distinct conditioned fear reaction sets in as a result of combination of sound and electrical stimulation of brain structures, which evoke defensive behaviour. The data obtained are analyzed in the light of the significance of natural requirements of the organism for the elaboration of conditioned reflexes.     

Conditioned reflex changes in the intra-analyzer interaction of the afferent inputs from the lateral geniculate body and pulvinar thalami in the cerebral cortex of cats

Paired heterogeneous stimulation of the lateral geniculate body (LGB) and pulvinar (Pulv) as a conditioned stimulus of alimentary instrumental conditioned reflex (CR), resulted in a change of relations between afferent inputs from LGB and Pulv to the visual and associative cortex of cats. At stimulation of LGB preceding by 40 ms, facilitation of the response to testing Pulv stimulation observed in untrained cats, appeared only at the beginning of the learning and was suppressed by the end of elaboration, when the amplitude of the response to the conditioning LGB stimulation greatly increased. In the process of CR elaboration (in the middle of learning), Pulv stimulation preceding by 40 ms facilitated the response to the testing LGB stimulation and simultaneously increased the amplitude of the response to the conditioning Pulv stimulation.     

The functional role of neurospecific protein S-100 in memory processes]

Elaboration of alimentary conditioned reflex in rats is accompanied by an increase of the level of protein S-100 in the left and right cerebral hemispheres. Amnestic factor M-cholinolytic atropine disturbs the elaborated habit and simultaneously decreases the quantity of protein S-100 up to the level of unlearned animals. The elaboration of conditioned reflex of passive avoidance does not change the content of protein S-100 in the rats brain. Intracisternal injection of antiserum to protein S-100 has an expressed amnestic action. Intracisternal injection of protein S-100 against the background of amnestic action of cholinolytic does not lead to restoration of memory. The cholinolytic and antiserum to protein S-100 mutually potentiate the amnestic effect.     

Neuronal activity of the cerebral cortex in cats with conditioned inhibition

Unit activity of the somatosensory cortex was studied in chronic experiments on cats during alimentary instrumental conditioned reflex performance and elaboration of conditioned inhibition (CI). First presentations of the CI signal at the beginning of CI formation caused, due to orienting reaction to a new stimulus, a levelling of the response of the neurones to the positive conditioned signal included into the CI complex. At the stage of consolidated CI, this depression proceeded gradually during the development of conditioned inhibition caused by consecutive presentations of the nonreinforced CI combination. Two groups of neurones were involved in the process of the CI performance: one of them being the same which was activated also in response to positive stimulation during performance of the conditioned response, and the second one being areactive to the positive conditioned stimulus but reducing the frequency of the background activity.     

Conditioned reflex switching over in unrestrained dogs

Conditioned switching-over was studied in unrestrained animals by means of instrumental alimentary conditioned reflexes of pressing the pedal. A complex of auditory and spatial factors (start-ground) served as conditioned alimentary signal. Backward connections were stable and were manifested in the teturning of the animal to the start-ground after feeding. It has been confirmed that the observed working readiness is a conditioned reflex of a tonic type.     

Dynamics of the spectral composition of the hippocampal theta-rhythm in the dog during switching-over of heterogeneous instrumental reflexes

In two dogs with electrodes chronically implanted in the hippocampus, hippocampal electrical activity and the heart rate were recorded in the process of elaboration of a conditioned switch-over of operant alimentary and defensive responses. Averaged computerized spectral characteristics of hippocampal theta-rhythm were essentially different between the alimentary and defensive situations in intersignal period as well as during the action of triggering conditioned stimulus. Individual differences in the dominant frequency of bioelectrical activity were observed. The animal with a higher theta-rhythm frequency elaborated conditioned switch-over of heterogeneous operant responses sooner and more successfully.     

The noradrenaline and serotonin content in symmetrical parts of the normal rat brain and during learning and peptide administration]

Content was compared of noradrenaline (NA) and serotonine (5-OT) in the right and left halves of the rats brain in norm, at elaboration of defensive conditioned reflexes of two-ways avoidance (CRTWA) and at administration of neuropeptides influencing the learning and memory--dezglycilargininvasopressin (DG-AVP), ACTH4-7 pro-gli-pro and dalargin. The conducted studies showed that in control animals the content of NA in the cortex of the right hemisphere was significantly higher than in the cortex of the left one. For the content of 5-OT in symmetric brain parts no significant differences were revealed. Under the elaboration of CRTWA the asymmetry of NA content was not eliminated. Systemic administration of DG-AVP, ACTG4-7 pro-gli-pro and dalargin practically did not change the content of 5-OT, but reduced the content of NA in the cortex and the rest of the brain, and the content of NA in the right and left cortex was equalized. The obtained data point to the asymmetric character of neuropeptides action and to greater resistance of 5-OT-ergic brain system to functional load and to administration of peptides in comparison with NA-ergic system.     

The effect of direct stimulation of the dog lateral hypothalamus on transformation of a passive-defensive situational reflex into an alimentary one]

The behavioral effect of electrical stimulation of the lateral hypothalamus with a current of equal parameters in chronic experiments on dogs depended on the signal significance of the surroundings. Stimulation of the lateral hypothalamus against the background of a defensive situational reflex in dogs which were in an experimental situation for the first time, far from evoking orientation to food and the act of feeding, enhanced the background fear reaction. After transformation of the defensive signal significance of the situation into an alimentary one, stimulation of the lateral hypothalamus began to activate the alimentary instrumental reflex and the act of feeding. However, at first the former was manifested irregularly. Combinations of stimulation of the lateral hypothalamus and achievement of the alimentary instrumental reflex with subsequent reinforcement stabilized and enhanced the alimentary instrumental reflex to the stimulation of the lateral hypothalamus.     

Interhemispheric asymmetry in rats differentiating figures by size

Motor alimentary conditioned reflex was elaborated in Wistar line rats to presentation of various pairs of figures, those of larger area serving as positive signals. In tests on animals with intact brain and with unilateral hemispheric cortical inactivation, new pairs of figures were used besides basic stimuli. The level of analysis in testing experiment was lower than normal: by 5.6% at intact brain, by 16.4%--at right hemisphere inactivation, by 36.4%--at left hemisphere inactivation. Elimination of the left hemisphere produced prolongation of the conditioned reaction time, signs of frustration and aftereffect. In conditions of right hemisphere inactivation the level of discrimination of figures depended on their specific properties and the side of presentation. Conclusion is made on dominating role of the left hemisphere in analysis of abstract and concrete characteristics of visual stimuli, in control of temporal, spatial and emotional characteristics of reactions in situations when considerable abstraction and distinguishing of generalizing invariant sign "more-less" is necessary for elaboration of the conditioned reflex.     

Effect an ACTH analog on the processes of learning and memory in rats

On the basis of the idea of the important role of neurotransmitter systems in realization of neuropeptide effects, the participation was studied of the monoaminergic systems in the mechanisms of the ACTH analogue influence on the processes of learning and memory in control animals and animals with a changed functional state of the monoaminergic systems. In parallel the influence was studied of the ACTH analogue on the content of the endogenic monoamines in various brain structures of rats. It has been shown that administration of the ACTH analogue in a dose of 10 mcg affects the elaboration and preservation of conditioned reflexes (CRs) of passive avoidance, CRs of two-side avoidance and labyrinth CRs only in conditions of changed functional state of the monoaminergic systems. Amnesia, usually elicited by 5-oxytryptophane and disulfiram is prevented by administration of the ACTH analogue. Administration of the ACTH analogue is accompanied by the intensification of serotonine metabolism in the midbrain and medulla and by an increase of noradrenaline content in the hypothlamus.     

Formation of temporary connections in dogs following destruction of the amygdaloid complex, head of the caudate nucleus and orbital cortex]

Ablation of the orbital cortical zones in dogs after ablation of the basolateral part of the amygdala and the caudate nucleus head considerably impeded the elaboration of secretory conditioned alimentary reflexes, without affecting the rate of elaboration of simple instrumental food-procuring reaction. The dogs lost however the capacity to differentiate non-reinforced stimuli from reinforced ones, which was revealed in both secretory and instrumental reactions.