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.     

Significance of the relative position in space of associated stimuli for formation and performance of motor conditioned reflexes

In experiments on cats the rate of formation of conditioned reflexes to sound (running to the feeding trough) depended on the spatial interrelations of the paired stimuli: the closer the source of the conditioned signal to the feeding trough, the sooner the formation of the conditioned reflex. It has been assumed that during formation of a conditioned reflex the closing of connection between conditioned and unconditioned stimuli is also attended with the closing of connection between the spatial parameters of the paired stimuli. Experiments with inactivation through cold of the temporal area (cortical representation of the vestibular system) of one hemisphere have shown that such a connection is formed in central parts of the vestibular analyser. When the conditioned reflex is elaborated to one feeding trough, the connection is duplicated by both hemispheres; in reflexes to two feeding troughs (i.e. spatial choice) such connections are lateralized in each hemisphere.     

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.     

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.     

Complex perception of stimuli during conditioning

The review concerns the effects of a variety of stimuli on the reproduction of conditioned reflexes. By the literature data, during conditioning of any type, besides the single stimulus intentionally applied by an experimenter as a conditioned one, an animal perceives the whole complex of stimuli (acoustic, visual, olfactory, algesic, and other exteroceptive, proprioceptive, and interoceptive stimuli), including those of the environment and time of the day during training. Many of these stimuli are essential for the reproduction of the acquired habit. The complex of stimuli that act on an animal during the reproduction should in all parameters correspond to that perceived by the animal during training. If the complexes differ at least in one stimulus, the reproduction of the reflex may fail.     

Characteristics of higher nervous activity in the suslik Citellus fulvus during its active period

In experiments on active ground squirrels, it was possible to form motor defensive conditioned reflexes and to re-arrange the conditioned reflexes from visual and auditory analysers. It was originally demonstrated that repetitive alteration of the informational content of the conditioned stimuli results in neurotic disturbances in animals.     

Features of the formation of conditioned secretory reflexes in response to the stimulation of different areas of the caudate nucleus of the dog

Properties were studied of elaboration of conditioned alimentary secretory reflexes to threshold electric stimulation of the caudate nucleus in dogs. The rate of formation of such a reflex and its magnitude were considerably lower than in reflexes elaborated to distant stimuli. Latencies were longer; dynamics of conditioned and unconditioned secretory reactions was similar to that of reflexes to a weak stimulus--light. The motor component of the conditioned alimentary reaction, as a rule, was absent. Characteristics were revealed of formation of alimentary reflexes to stimulation of the dorsal and ventral parts of the head and body of the caudate nucleus.     

Effect of a cyclic analog of enkephalin on learning and memory in the mouse

In experiments on mice, the effect of cyclic analogue of enkephalin (CAE) on the processes of learning and memory was studied in control animals and in animals with changed functional state of monoaminergic brain systems. Administration of the peptide to intact animals significantly accelerated the acquisition of conditioned reflexes of two-way avoidance and did not significantly affect the retention of these reflexes and their subsequent reproduction. Retention and reproduction of conditioned reflexes elaborated in one combination, was disturbed. Administration of iprazid did not eliminate the "accelerating effect" of CAE on the formation of conditioned reflexes of the two-way avoidance but sharply disturbed their retention. In such conditions, the amnesing iprazid effect increased still more. Besides, under CAE effect, the activity of acetylcholinesterase in the motor and especially in the visual cortex of the mice increased. The obtained data testify to an important role of the monoaminergic and cholinergic brain mechanisms in realization of CAE effects on the processes of learning and memory.     

Vector representation of associative learning

I. P. Pavlov [12] has shown that conditioned reflexes are selective both with respect to conditioned stimuli and to conditioned reflexes elicited by those conditioned stimuli. At the neuronal level selective aspects of conditioned stimuli are based on detectors selectively tuned to respective stimuli. The selective aspects of conditioned reflexes are due to command neurons representing specific unconditioned reflexes. It can be assumed that conditioned reflexes result from association between selective detectors and specific command neurons. The detectors activated by a conditioned stimulus constitute a combination of excitations--a detector excitation vector. The detector excitation vector acts on a command neuron via a set of plastic synapses--a synaptic weight vector. Plastic synapses are modified in the process of learning making command neuron selectively tuned to a specific conditioned stimulus. The selective tuning of a particular command neuron to a specific excitation vector referred to a conditioned stimulus is a basis of associative learning. The probabilities of conditioned reflexes elicited by conditioned and differential stimuli implicitly contain information concerning excitation vectors that encode respective stimuli. Contribution of the vector code to associative learning was explored combining differential color conditioning with intracellular recording from color-coding neurons. It was shown that colors in carps and monkeys are represented on a hypersphere in the four-dimensional space similar to human color space. The basis of the color space is constituted by red-green, blue-yellow, brightness and darkness neurons.     

Importance of traces of a preceding unreinforced stimulus to the formation of inhibitory conditioned reflexes in the rat

The results of experiments with the inhibitory signal presented to rats after the positive one, showed the significance of the negative signal memory trace which interrupted alimentary behaviour and considerably accelerated its full extinction in response to the previously positive signal. Its significance is shown in experiments with amnesia produced by electroshock. According to the suggested concept negative conditioned reflexes are a result of formation of a temporary connection between memory traces of the negative conditioned signal and the non-reinforcement of this signal.     

Correlation of the neuronal impulse activity of different areas of the neocortex in rabbits in the switching of positive and inhibitory conditioned reflexes

By cross-correlation method conjugation in impulse activity of pairs of simultaneously recorded units in the visual and sensorimotor areas of the neocortex (representations of the conditioned and unconditioned stimuli) was studied during the switching of defensive positive and inhibitory reflexes in rabbits. 30-second fragments of impulse activity were analyzed in intervals before and after three presentations of positive and inhibitory conditioned stimuli (CS). The activity of single pairs of units in the process of stimuli presentation was characterized by instability. Only in 29% of 51 units' pairs the presence or absence of correlation between their discharges was stable. Analysis of activity of 75 pairs of units showed differences in impulse activity in inhibitory and positive tonic reflexes. The number of pairs of correlated units in about 30 s after inhibitory CS decreased (27%) in comparison with the interval before its action (52%). In the inhibitory tonic conditioned reflex, temporal intervals of discharges of one unit correlated with discharges of the second unit undergo changes. The obtained results testify that such parameter as the number of pairs of units with correlated activity in intersignal time interval is very important for the realization of motor reaction to conditioned stimuli.     

On neurotransmitter mechanisms of reinforcement and internal inhibition

Experiments reported in this study have been performed in order to investigate cholinergic and GABA-ergic neurotransmitter systems and substance P in the realization of internal inhibition and pain reinforcement. This was accomplished during the elaboration of inhibitory and defensive conditioned reflexes to light flashes in alert, nonimmobilized rabbits. Present results together with a review of past research indicate that the cholinergic system is directly involved in transmitting the effects of pain reinforcement to neocortical neurons. Substance P, a neuropeptide, reduces the background activity of neocortical and hippocampal neurons and the response of cortical neurons to pain and positive conditioned stimuli. The cholinergic system and substance P exert a modulating effect on the elaboration of internal inhibition. Phenybut, a GABA derivative capable of penetrating the blood-brain barrier, enhances inhibitory hyperpolarization in the cerebral cortex and improves discrimination between the inhibitory and reinforcing light flashes. It appears, therefore, that the GABA-ergic system plays a leading part in the elaboration of internal inhibition. Neuronal activity and slow potential changes in response to positive conditioned and pain stimuli occur in the same direction after administering the preparations, and the dynamics of these changes is different from that in responses to inhibitory stimuli. It may be supposed on these grounds that the neurotransmitter and neuromodulator systems studied possess a considerable degree of plasticity.     

Newly revealed range of action in the preparation derinat: Mnemotropic effect

Mnemotropic effect has been revealed in the action of Derinat, a biologically active compound of natural origin, on the formation of conditioned reflexes of active and passive avoidance. Derinat accelerates the elaboration of conditioned reflexes. This effect manifests itself already at initial stages of the elaboration, which resembles the effect produced by nootropics.     

Involvement of mesencephalic reticular formation neurons in cat conditioned reflexes

Traditional defensive and operant food reflexes were used to investigate neuronal responses of the mesencephalic reticular formation. It was found that these neurons may be divided into different groups according to function, depending on how they respond to positive conditioning stimuli. Of the two main groups of neurons with sustained tonic reactions one is activated in response to positive acoustic conditioning stimulation; it no longer reacts to the same stimulus after extinction of the reflex, while the other only becomes involved in response to positive stimulation accompanying the initiation of movement. Neurons belonging to the second group begin to respond directly to acoustic stimulation after extinction of the conditioned reflex. Neurons of the mesencephalic reticular formation can thus exercise additional tonic ascending effects both in the production and inner inhibition of the conditioned reflex. The group of neurons with a phasic reaction, i.e., a double response (a direct response to sound and another produced by movement) displayed a drop in spontaneous activity during the shaping of inhibition of differentiation and of extinction in particular. It was found that the initial changes in the spike response of reticular formation neurons during conditioning and pseudo-conditioning are similar. There are thus grounds for stating that neurons of the mesencephalic reticular formation participate in the shaping, production, and inner inhibition of traditional and operant conditioned reflexes in a differentiated capacity rather than as a population reacting identically.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 2, pp. 161–171, March–April, 1986.     

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.     

Role of monoamines in the recovery of the conditioned reflex activity of rats following extirpation of the frontal cortex

The influence of frontal cortex extirpation on the amount of monoamines in the brain structures was investigated in chronic experiments on rats trained according to the method of motor feeding reflexes with bilateral reinforcement. Monoamine levels were measured by high performance liquid chromatography with electrochemical detection. By the ninth day after the ablation serotonin (5-HT) and dopamine (DA) levels were significantly reduced in the cortex and the striatum, respectively, while noradrenaline ++ (NA), 5-HT, dihydroxyphenylacetic and 5-hydroxyindoleacetic acid levels in raphe nuclei and locus coeruleus were increased. The level of conditioned reflex reproduction was 39% on the light and 33% on the sound stimulus. The involvement of monoamines in the recovery of conditioned reflexes after frontal cortex extirpation is discussed.     

Formation, fixation and reproduction of temporary connections during adaptation to physical loading

It is shown that long-term adaptation to physical loads of various intensity and duration has an influence on formation, fixation and reproduction of temporary connections in rats. Periodicity of conditioned activity has been found in the process of protracted training. After twenty days of adaptation to submaximal physical loads, the processes of fixation and reproduction of temporary connections improve whereas with elongation of adaptation the conditioned activity somewhat deteriorates. In conditions of long-term training by maximal physical loads, both elaboration and preservation of conditional reflexes in all adaptation terms is affected.     

Effect of fenamin and haloperidol on conditioned activity of neurons of the motor cortex and striopallidal system

The activity of neurones in the motor cortex, caudate nucleus, putamen and globus pallidus was studied during elaboration of motor conditioned reflexes to time in rabbits, treated with 1-amphetamine and haloperidol. Mechanisms of reproduction of cells trace activity in the reflex to time at the omission of trials, reacted to 1-amphetamine by increasing the intensity of reactions in the motor cortex and inactivation in putamen cells. The curve of dynamics of intensity changes of trace discharges in the course of a series of trials omissions remained unaltered only in motor cortex; in the other structures it significantly differed from the norm of intact animals. Haloperidol depressed the mechanisms of reproduction of trace reactions of the globus pallidus cells, and made them almost fully inactive in the motor cortex; the putamen neurones reacted to haloperidol by an increase of trace reactions intensity. Against the background of the animal chronic 1-amphetamine intoxication, haloperidol normalized the dynamics and intensity of trace activity. "Therapeutic" effect of haloperidol was most distinctly expressed in the motor cortex and putamen cells, less--in the caudate nucleus and was completely absent in the globus pallidus.     

Systems mechanisms of internal inhibition

The state of internal inhibition is analysed which is considered as a multifactor systemically organized process. On model of combined presentation of positive and inhibitory stimuli in experiments on white rats and dogs, a dependence is established of the efficiency of reinforcement cancellation factor on motivation intensity. Condition of negative emotion--frustration, "difficult state"-is a necessary link in the process of internal inhibition formation, since it is responsible for selection of non-reinforcement for storage in the long-term memory. Conclusion is made that active inhibition of goal-directed behaviour is mediated by actualization of memory trace, "engram of non-reinforcement" by negative conditioned stimulus.     

Effect of the preparation baliz-2 on the integrative brain activity and biogenic amine metabolism in rats under stress

Effects of balis-2 on exploratory activity in the open field and elevated plus-maze, attention to sensory stimuli of different modalities, elaboration and retention of conditioned reflexes with food reinforcement, were studied in rats under stress. Prolonged treatment of rats with balis-2 seems to normalise integrative activity and metabolism of serotonine and dopamine in the animal brain.