Spatiotemporal distribution of conditioned evoked potentials during latency of inhibition in cats

Using a model of slightly delayed defensive conditioned reflexes in cats during acute experiments, reproduction of the memory trace was investigated in several brain structures after pre-exposure to a conditioning stimulus. The memory trace was recorded in the form of its electrographic correlates, i.e., of conditioned evoked potentials, conditioned neurographic response in the peripheral nerve, and conditioned galvanic skin response. Findings showed that prior presentation of isolated nonreinforced conditioning stimuli completely blocked the reproduction of condition evoked potentials in the auditory cortex and the zona incerta, as well as conditioned neurographic response. Production of the galvanic skin reaction (the vegetative component of the conditioned reflex) was sharply autonomic. It was concluded that the spatiotemporal structural organization of the brain, essential for complete reproduction of the conditioned reaction, was suppressed during latency of inhibition.Institute of Physiology, Siberian Branch, Academy of Medical Sciences of the USSR, Novosibirsk. Translated from Neirofiziologiya, Vol. 17, No. 5, pp. 640–645, September–October, 1985.     

Effect of a change in the effectiveness of a benzodiazepine-GABA-ionophore complex blockade on the reproduction of an amnesic memory trace in mice after preliminary diazepam administration

The paper deals with the results of analysis of the influence of blocked of BD-GABA-ionophore complex and its separate components on recover of memory trace amnesia during BD-receptors activation in experiments on elaboration of CR of passive avoidance in mice. It is shown that at "neurochemical tuning" the improvement of conditioned reaction reproduction on the 2-nd and 21-st day after learning and amnestic action was observed only at GABAA receptor blockade by bicuculline, while the blockade of BD-receptor by flumazepil and of chlorine channel by picrotoxin was ineffective. Simultaneous blockade of all BD-GABA-ionophore complex components was not more effective in comparison with the blockade of its separate links in the recovery of conditioned reaction reproduction. The presented data allow to suppose that "psychogenic" amnesia development is determined by the functional state of neurotransmitter brain systems at learning and amnestic action which stipulates subsequent possibility of memory trace retrieval.     

Changes in trace reactions of sensorimotor cortex and putamen neurons as affected by haloperidol

Experiments on conscious rabbits were made to elaborate motor conditioned reflexes through pairing stimuli with electrocutaneous reinforcement applied every 30 s. Neuronal activity in the sensorimotor cortex and putamen was recorded during formation and reproduction of the conditioned reflexes before and after haloperidol injection (0.2 mg/kg i. v.). In the putamen, haloperidol increased the number of neurons exhibiting trace conditioned activity and made the intensity and duration of these processes rise. The changes seen in the sensorimotor cortex were opposite in nature. Inhibition of trace conditioned activity in the sensorimotor cortex depended mainly on the decreased amplitude of the reaction conditioned component. The role of the dopaminergic system in the interaction of the neostriatum and sensorimotor cortex and in formation and reproduction of trace conditioned activity of both the structures is discussed.     

Characteristics of the conditioned reaction of passive avoidance in rats after destruction of the terminal dopaminergic fields in the amygdaloid complex

Character of conditioned reaction of passive avoidance was analyzed in Wistar line male rats after neurochemical destruction of terminal dopaminergic fields of the amygdalar complex. 6-hydroxydopamine was bilaterally administered to the central nucleus of the amygdalar complex after preliminary treating with desmethylimipramine for selective destruction of dopaminergic terminals. Lowering of dopamine level in the amygdalar complex led to a weakening of reproduction and to prolongation of spontaneous extinction of conditioned reaction. Features of conditioned reaction are highly similar to the effect of latent inhibition connected with attention deficit. It is suggested that activity of terminal fields of the amygdalar complex is one of the mechanisms providing for attention and intensifying selection of information in learning.     

The effect of iproniazid on biogenic amine levels, elaboration and reproduction of alimentary conditioned reflexes]

A study of the action of iproniaside on alimentary conditioning has shown that even its small doses (25 mg/kg) disturb the formation of the conditioned reaction, while large doses (200-250 mg/kg) do not disturb the reproduction of the conditioned reaction elaborated and stabilized before the administration of the drug. Hence, dissociated learning with the use of iproniaside is impossible. The applied doses of iproniaside result in an increased level of biogenic amines in the dopaminergic nigro-neostriate and reticulo-septal brain systems. It is therefore assumed that the effects of iproniaside on learning are due to its influence on the level of the CNS biogenic amines.     

The role of the lateral and medial hypothalamus in reproducing a motor reaction as the signal during the acquisition of classical conditioned reflexes]

In experiments on three dogs there was shown that testing electrostimulation of the lateral hypothalamus reproduced the motor reaction which is a signal stimulus at elaboration of classic alimentary conditioned reflexes (CRs) and did not reproduce it at elaboration of classic defensive CR. Testing electrostimulation of medial parts of the hypothalamus reproduced, as LH electrostimulation the "signal" motor reaction, but in less percentage of cases, during elaboration of classic alimentary CRs and did not reproduce it at elaboration of classic defensive CRs. The reproduction of the signal motor reaction at LH electrostimulation is connected with activation of backward conditioned connection from motivation structures of the hypothalamus to representation of the signal stimulus in the motor cortex.     

The dynamics of latent inhibition in rats under the action of substance P]

The role of substance P in latent inhibition was studied in experiments on rats. Administration of neuropeptide during pre-exposition of conditioned stimulus and before conditioning disturbed all signs of latent inhibition: level of reproduction, retention and resistance to amnestic action of conditioned reaction in the task of passive avoidance. Single administration of haloperidol before learning prevented the disturbance. Significance of hyperfunction of substance P in selective attention and pathogenesis of schizophrenia is discussed.     

Effect of diazepam on the formation of temporal connections by means of recognizable visual stimuli

In emotionally labile persons the role of the limbic link in the structure of temporary connections formed by means of a realized emotionally significant word, was studied with the help of diazepam. The diazepam turned out to be an effective agent for studying the mechanisms underlying the formation and reproduction of temporary connections in man. Against the background of its action it is not possible to elaborate a conditioned cortical reaction on emotionally significant reinforcement. This is connected by the authors with predominant action of this tranquilizer on formations of the limbic system.     

Radiation resistance of motor-defensive conditioned reflexes in rats at different stages of the formation and stabilization of a temporary connection

Disturbances were studied of the motor defensive conditioned reflexes in rats radiated in a dose of 100 Gy at different stages of formation and stabilization of temporary connection. In comparison with consolidated (automatized) conditioned reflexes of active avoidance, early stages of formation and stabilization of the temporary connection are characterized by a relatively low resistance against extreme factors and by deepest disturbances of reproduction in radiated animals. The most probable mechanisms of these disturbances are connected with pathological changes of the nervous processes balance towards an increase of excitability and weakening of internal inhibition. Yet a direct radiation influence on the mechanisms of temporary connection reproduction at the second stage of its consolidation cannot be excluded. The role is shown of the emotional reactivity in the above-described processes.     

Comparative analysis of the antiamnesic action of a blockade of the benzodiazepine-GABA-ionophore complex and of an activation of the dopaminergic system in the brain of mice

In experiments on mice by the method of conditioned reaction of passive avoidance and amnesia elicited by the animal delay in the dangerous compartment immediately after electrocutaneous stimulation, antiamnestic effect is demonstrated of pharmacological influences, changing the activity of benzodiazepine-GABA-ionophore complex and dopaminergic system. Comparative analysis of the efficiency of neuropharmacological substances of different actions on synaptic apparatus of the studied transmitter systems in amnesia reduction showed that the greatest effect of improving the reproduction of the conditioned habit was that of the bupropion, the highly specific blockator of dopamine reverse absorption. The obtained results testify that amnesia development is based on activation of the inhibitory GABAergic brain processes and disturbance of dopaminergic system functioning.     

Reproduction of electrographic correlates of a conditioned reflex after changes in the activity of the noradrenergic and dopaminergic systems

On the model of shortly delayed defensive conditioned reflex in cats, it was shown in acute experiments that pharmacologically elicited change of NA system activity (clonidine, 0.2 and 1.5 mg/kg intravenously) and of DA system activity (apomorphine, 3 mg/kg intravenously) leads to a definite manifestation of electrographic correlates of memory trace, i.e. of conditioned evoked potential (EP) in examined brain structures, as well as of conditioned neurographic response (CNR) and conditioned skin-galvanic reaction (SGR). The increase of the NA system activity causes a rise of the number of conditioned EPs in the reticular formation, hippocampus and preoptic area along with an enhancement of CNR reproduction. The increase of the DA system activity contributes to the appearance of conditioned EPs in the hippocampus, amygdalar complex and central gray matter, together with an enhancement of the reproduction of conditioned SGR.     

The retroactive action of paradoxical sleep deprivation and immobilization stress on the mechanisms of memory and passive avoidance in rats

Influence was studied of 48-hours deprivation of paradoxical sleep (DPS) and immobilization stress on conditioned reaction of fear and security--components of passive avoidance conditioned reflex (CRPA), with simultaneous studying of vertical, horizontal activity, grooming reactions and defecations in an illuminated chamber. The obtained results allow to conclude that DPS inhibits reproduction of memory traces of fear reaction but intensifies the process of learning and activity of memory traces of security reaction. Depending on condition of CRPA elaboration, DPS may disturb or, on the contrary, prolong preservation of passive avoidance. It has been found that the immobilization stress does not influence CRPA preservation and does not weaken the reaction of fear but increases the horizontal activity. It is suggested that the observed changes in behaviour and trace processes are connected with disturbance of sensory informational homeostasis of the nervous system at DPS.     

Effect of benzodiazepine receptor blockade on memory processes in the mouse

The results of study testify to a stimulating effect of benzodiazepine receptors blocators RO15-1788 and RO15-3505 on reproduction of conditioned reaction of passive avoidance in mice disturbed as a result of various procedures-"psychogenic" and cycloheximide amnesia, extinction and forgetting. A considerable antiamnesic effect of the drugs on cycloheximide amnesia models is noted, in comparison with the "psychogenic" one. RO15-3505 is more effective in the processes of extraction of memory traces under amnesia. The obtained results testify to an important contribution of benzodiazepine-GABA-ergic brain systems in inhibitory regulation of the processes of stored memory traces reproduction.     

Interaction of the serotoninergic and GABA-ergic systems in "psychogenic" amnesia

The results are analyzed of the influence of blockade of separate components of BD-GABA-iontophoretic complex on activation of memory-trace amnesia under blockade of serotonine PGA synthesis in experiments with conditioned reaction (CR) of passive avoidance in mice. It has been shown that the blockade of serotonine PGA synthesis did not change the behavioral manifestations of amnesia at all terms of testing. The blockade of chlorine channel by picrotoxin and of BD receptors RO15-1788 and RO15-3505 restored the reproduction of the memory trace disturbed against the PGA background; the blockade of GABAA-receptors by bicuculline lost its effectiveness. Activation of serotonin system by sertraline against the PGA background before learning and amnestic influence or before testing of CR of passive avoidance contributed to restoration of CR activating action of bicuculline. It was found that preliminary blockade of PGA serotonine synthesis changed the amnesia development and the character of subsequent restoration of CR of passive avoidance reproduction by blockaders of separate components of BD-GABA-iontophoretic complex.     

Effect of cadmium chloride on the processes of learning and memory in rats

Intraperitoneal injection of cadmium chloride (4 mg/kg) to rats before elaboration or reproduction of two-way avoidance conditioned reflex (TACR) disturbs both these processes. Deterioration of elaboration does not affect connections fixation and their subsequent reproduction. Injection of the substance before the elaboration of passive avoidance conditioned reflex (PACR) depresses elaboration and consolidation. Injection of cadmium chloride before testing of PACR preservation does not influence the processes of engrams reproduction. The observed disturbances cannot be connected with changes of animals motor activity.     

Effects of distant transplantation of the embryoniclocus coeruleus on the learning process and memory in rats

We studied the effects of distant transplantation (in the neck region, subcutaneously) of the embryoniclocus coeruleus tissue on the indices of the learning process and memory in recipient rats. The patterns of learning for a conditioned emotional avoidance reaction (CEAR) allowed us to classify experimental animals into two groups, with successful and hampered formation of the CEAR sterotype, respectively. In the first-group rats, after formation of this stereotype we electrolytically injured the frontal brain cortex, which resulted in some worsening of the CEAR reproduction and quality of differentiation. Distant transplantation of thelocus coeruleus tissue provided effective recovery of the CEAR reproduction in the first-group animals, while rather fast and successful formation of the CEAR stereotype became possible in the second group of rats. It is concluded that the transplantedlocus coeruleus tissue preserves its viability, undergoes differentiation, and exerts a stimulating influence on the learning process and memory formation (probably, due to activation of noradrenergic links in the brain systems).     

Conditioned reactions of hippocampal neurons during amphetamine poisoning and its counteraction with haloperidol

Activity of 144 neurones of the dorsal part of the rabbits hippocamp was recorded during elaboration of motor conditioned reflex to time. Chronic amphetamine intoxication lowered the ability of hippocampal neurones to form conditioned reactions in response to pairings of sound stimuli with electrocutaneous reinforcement and fully suppressed mechanisms of reproduction by cells of engrams of previous pairings in series of their omissions Single administration of haloperidol to intact animals somewhat increased the number of neurones reacting to the pairing and their omissions in conditioned reflex to time without significantly influencing the intensity and dynamics of reproduction of endogenous cellular reactions in the series of consecutive omissions of pairing. Haloperidol administration during amphetamine intoxication elicited shifts towards normalization of conditioned activity of neurones, eliminating the suppressing action of amphetamine on mechanisms of reproduction of engrams of combined stimuli. Such "therapeutic" effect of haloperidol in many cases did not depend on the character of its psychotropic action. The properties of amphetamine and haloperidol action on the cells of the hippocamp are discussed as compared to their action on the neurones of other brain structures, previously studied in an analogous experimental situation.     

Analysis of the participation of rat brain noradrenergic terminals in elaboration of conditioned passive avoidance response]

A change in a noradrenaline concentration in the noradrenergic terminals was investigated by the fluorescent histochemical method in pars ventralis nuc. interstitialis striae terminalis, nuc. septi lateralis and in nuc. preopticus medialis of male Wistar rats in the process of reproduction of conditioned passive avoidance response. In all the investigated structures of the preliminarily trained animals the reproduction of a conditioned response (without any electrical stimulation) led to a statistically reliable decrease in the noradrenaline concentration. The data obtained testified to the participation of the noradrenergic brain system in the reproductive process of the conditioned passive avoidance response.     

Dynamics of the formation, reproduction and recognition of trace conditioned reflexes to positive and negative stimuli

The dynamics of formation, reproduction, and recognition of trace conditioned reflexes to positive and differentiation stimuli was studied on subjects of 15-17 years old. Formation and reproduction of such reflexes was found to occur under a close interaction of both levels of the higher nervous activity--recognized and unrecognized levels. Recognized reactions prevailed on unrecognized ones in cases of involvement of active attention. On the basis of this fact, the formation and reproduction of trace conditioned reflexes to positive stimuli has been supposed to occur with an active participation of the left hemisphere. The right hemisphere apparently plays a leading role in formation and reproduction of trace conditioned reflexes to differention stimuli to which the attention of the subjects was not fixed.     

The role of different neuromediator systems in regulating the reproduction of memory engrams in rats

In experiments on 796 white rats the role was studied of various neurotransmitter systems (choline-, adreno-, serotonin-, dopamine-, and GABA-ergic) in regulation of processes of engrams reproduction, determined by tests of conditioned passive- and active-defensive reactions in comparison with changes of spontaneous motor activity and oriented reaction. Correlations are analyzed between the changes of animals behavioural reactions in conditions of pharmacological control of activity of the studied neurotransmitter systems.