[Role of the motor cortex in the control of axial and proximal muscles in learning].

Involvement of the motor cortex in the control of the shoulder and the scapula muscles was studied during acquisition of the novel head-forelimb coordination in dogs. The dogs were trained to raise the forelimb fixed to the lever in order to lift a food-containing cup and keep it elevated during eating with the head tilted down to the feeder. At the early stage of learning, the movement of raising the limb occurred with an anticipatory upward head tilt, whereas the head tilt to the feeder was associated with the lowering of the raised limb. Food consumption required a new coordination, i.e., maintaining the raised limb in a posture with the head lowered. This coordination could only be achieved by learning. This new coordination was critically dependent on the intact motor cortex. It was found that in the natural coordination, raise of the limb involved regular activation of the main flexors of shoulder, i.e., deltoid and teres major muscles, and inconstant participation of teres minor, supra- and infraspinatus, trapezius muscles. Muscles of the latter group were often active during standing but ceased their activity before limb raise. The learned limb raise with the head tilted down occurred with activation of all the mentioned muscles, and some of them changed their activity for the opposite pattern. Lesions in the motor cortex (inclusive the main part of the projection area of the "working" limb) led to a restoration of the natural head-fore- limb coordination and the innate muscle pattern of the limb raise. Thus, in the course of learning, the motor cortex rearranges the innate pattern of coordination of phylogenetically old axial and proximal muscles, which begin to work in a new manner.

[Functional effects of transcranial electromagnetic stimulation (60 and 70 Hz) of the brain of intact rats and rats with acute brainstem damage].

Behavior and brain electrical activity of 79 male Wistar rats (intact and with acute experimental brainstem injury) were studied during the course of therapeutic transcranial electromagnetic stimulation (TEMS) with frequencies 60 and 70 Hz. In intact animals this effect was accompanied by a decrease in voluntary motor activity and increase in synchronization of the brain electrical activity, in particular, in the delta and beta1 frequency ranges. This inhibitory effect was similar to that of sleep. In the early period of acute experimental stem pathology, the TEMS course was accompanied by suppression of EEG signs of adaptive post-operative stress response and could lead to increased severity of the condition of an animal, along with the slowing of postoperative recovery. Cytomorphological evidence was obtained to the importance of vascular factor in the formation of cerebral reactions to TEMS.

[Correlation between activities of neurons of sensorimotor and visual cortices after forming a hidden focus of excitation (defensive dominanta) in cortical representation of a forelimb in rabbits].

The interaction between neurons of sensorimotor and visual cortices was investigated by cross-correlation analysis. In this interaction, we examined the role of sensorimotor neurons responding to light. In rabbits with a hidden focus of excitation, neurons of the sensorimotor cortex responding to light significantly more often formed correlation joints with cells of the visual cortex than neurons not responding to light. On the other hand, neurons of the visual cortex significantly more often formed correlation joints with neurons of the sensorimotor cortex not responding to light.

[Behavior of rats after immobilization and structural reorganization in the motor cortex and hippocampus].

Behavioral changes and accompanying morphological neuron-glia reorganization in the rat brain were analyzed after long-term immobilization. Wistar rats (n = 23) were stressed by interruptive immobilization, which was carried out within three week daily for 7-8 h. Behavioral immobilization of rats was accompanied by a decrease in the locomotor and exploratory activity in "open field" test and increase in the number and duration of freezing episodes. The morphometric studies revealed a statistically significant threefold increase in the density of hypoxic neurons in the motor neocortex of both hemispheres and CA3 field of the hippocampus in the experimental animals as compared to control. The number of glia cells in the motor cortex did not change. The increase in the density ofglial cells and multi-nucleolar neurons in CA3 region of the hippocampus are indicative of the compensatory processes in the brain. The hypoxic changes in neurons were of the functional character.

[Study of extracellular concentration of dopamine and its metabolites in mice striatum by a microdialysis technique at intraperitoneal administration of MPTP].

In this paper a structure of a microdialytic cannula inserted into brain areas just before a microdialysis is described. The cannula used allowed to find out a correspondence of behavioral and biochemical changes in C57BL/6 mice at various time intervals after a single dose administration (20 mg/kg) of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, without any additional pharmacological actions enhancing an extracellular striatal dopamine concentration. Immediately after 1-methyl-4-phenyl-1.2,3.6-tetrahydropyridine administration an essential disturbance of mice behavior and a significant reduction of the extracellular concentration of dopamine and homovanillic acid were observed in striatum. A week after the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration neither behavior nor the extracellular dopamine and homovanillic acid striatal concentration substantially differed from those of controls. 30 days after the neurotoxin administration there was again an essential disturbance of behavior and the large reduction of dopamine and its metabolite concentration in striatum. There was suggested that a reduction of the dopamine concentration immediately after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injection connected with abnormalities of dopamine synthesis and metabolism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine whereas a reduction of the extracellular striatal dopamine concentration 30 days after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration related to damage of the nigrastriatal dopaminergic system.

Comparison of the behavior of rats after immobilization with structural changes in the motor cortex.

Behavioral and neuronal-glial changes after emotional stress induced by discontinuous (7-8 h per day for one week) immobilization were compared in Wistar rats (n = 20). Immobilization led to increases in horizontal and vertical activity and the duration of "comfort" grooming in the open field test. Morphometric measurements demonstrated significant increases in the density of hypoxic neurons in the motor area of the right hemisphere of experimental animals as compared with measures in controls. Hypoxic changes in neurons were functional in nature. Experimental rats can be regarded as a model of the redistribution of brain functional activity with a preferential increase in the role of the left hemisphere.

[Effects of human and rat interferons-alpha on the behavior of rats of different ages. Comparative study of the homology of amino acid sequences].

Effects of chronic intranasal administration of human and rat interferons alpha on feeding and defensive behavior of rats were studied. Natural leukocyte human interferon "Lokferon" (a mixture of alpha interferon subtypes) and recombinant rat interferon alpha of the first subtype were used in the dose of 350 ME per rat daily. In addition, using the databases NCBI and EBI, we quantitatively estimated homology of amino-acid sequences between different subtypes of human and rat interferons. Both human (mostly in young rats) and rat interferons (mostly in old rats) increased rat feeding behavior after food conditioning to an audio tone. In old (but not in young) rats, both human and rat interferons worsened the ability of time interval assessment. In young (but not old) rats, both interferon kinds improved avoidance conditioning. The degree of homology between different human and rat interferons varied from 72% to 77%. Thus, generally, the effects of rat and human alpha interferons (350 ME) on rat conditioning were similar. This may be due to high degree of homology of amino-acid sequences between the two interferons.

[Correlation of the rat behavior after immobilization with structural reorganization in the motor cortex].

Behavioral changes and accompanying morphological neuron-glia reorganization in the rat brain were compared after emotional stress. Wistar rats (n = 20) were stressed by the interrupted immobilization, which was carried out during one week 7-8 h daily. Behavioral immobilization of rats was accompanied by an increase in horizontal and vertical locomotors activity and in duration of the III and IV phases of grooming ("comfortable" grooming) in the "open field" test. The morphometric studies showed a statistically significant increase in the density of hypoxic neurons in the right neocortex of the experimental animals as compared with control. Hypoxic changes in neurons were of functional character. Experimental rats can be considered as a model of redistribution of functional brain activity with preferential intensification of the left brain hemisphere.

Role of the motor cortex in the rearrangement of a natural movement coordination in dogs.

Chronic experiments on dogs were performed to study the activity of the shoulder muscles involved in elevating the forelimb used by the animal to lift a food-containing cup and keep it elevated during eating. At the early stage of acquisition of this operant reaction, limb-lifting occurred with an anticipatory upward head movement; lowering of the head to the feeder was associated with lowering of the lifted limb. The new coordination required for food to be obtained, i.e., maintaining the elevated limb in a posture with the head lowered, could only be achieved as a result of learning. In untrained dogs with the natural coordination, elevation of the limb occurred with activation of the deltoid and teres major muscles, teres minor being active on standing but ceasing its activity before limb elevation. During training the activity of the teres minor muscle changed to the opposite pattern. Limb elevation in the learned coordination was accompanied by activation of all three shoulder flexors. Lesioning of the motor cortex in the projection area of the "working" limb, but not in other areas, led to impairments of the acquired coordination and a new pattern of shoulder muscle activity. These data led to the conclusion that rearrangement of the initial coordination was linked with the formation of a new means of elevating the limb in which the muscle pattern was supported by the motor cortex.

[Study of the role of the right and left orbitofrontal cortex in compensatory cerebral reactions after acute brainstem damage].

Significance of the right and left orbitofrontal cortex (OFC) in recovery after acute brainstem lesion (at the level of n. Deiters) was investigated using rat model of complex brainstem-orbitofrontal cerebral damage. It was found that the right-side lesion of the OFC combined with isolated brainstem damage resulted in aggravation of the animal condition and highly probable lethal outcome within the first two weeks after surgery (because of the brain circulation disorder of hemorrhagic type). It may be associated with sympathetic activation. It is suggested that a certain "stimulation" of the left OFC (as the effect of its incomplete destruction) involves a parasympathetic compensatory reaction that allows animals with a severe brainstem pathology to survive. It is shown that, with the general nonspecific tendency to postoperative increase in emotionality, the greatest shifts in the emotional sphere take place under conditions of a combined damage of the brainstem and left OFC.

Role of the parietal associative area of the cortex for "counting" behavior in dogs.

Experiments were performed on six dogs to study the effects of simultaneous and separate ablation of fields 5 and 7 of the parietal cortex on "counting" behavior. Dogs were trained to discriminate series of five sound clicks presented with variable interstimulus intervals from similar series consisting of three clicks. A food-related operant response (elevation of the right forepaw to place it on the feeder) was used to develop asymmetrical differentiation; the positive signal was a series of five clicks with variable interstimulus intervals and the negative (unreinforced) stimulus was a series of three clicks. Simultaneous bilateral ablation of fields 5 and 7 of the parietal cortex, like bilateral ablation only of field 5, produced profound impairment of differentiation lasting 2-3 months. Isolated bilateral ablation of field 7 produced no impairment of differentiation. These data led to the conclusion that field 5 of the parietal cortex is important for discriminating the numbers of sequential signals.

[The role of the motor cortex in rearrangement of the innate movement coordination in the dog].

In chronical experiments in dogs the pattern of shoulder muscle recruitment was examined during the forelimb flexion by which the animal lifted and held a cup of food during eating. At the early stage of the instrumental reaction learning the forelimb lifting was performed with the anticipatory deviation of the head in up direction, when the head bent down to the foodwell the lifted forelimb lowered. Simultaneous holding of the flexed forelimb and lowered head providing food reinforcement was achieved only by learning. It was found that the forelimb lifting in the innate coordination in untrained dogs was performed with activation of m. deltoideus and m. teres major, whereas m. teres minor was active whilst the dog was standing but the muscle activity was abolished before the limb lifting. In the course of learning m. teres minor activity was changed into opposite one. In the learned coordination the limb lifting was accompanied by the activation of all three shoulder flexors. The lesion of the motor cortex in the area of the "working" forelimb, but not in other areas led to disturbance of the learned coordination and the novel pattern of the shoulder muscle activity. The data obtained led to the following conclusion: the rearrangement of the innate coordination is connected with the formation of the novel way of the forelimb lifting which pattern of muscle recruitment is provided by the motor cortex.

[Effect of small doses of interferon-alpha on food conditioning in young and ageing rats].

Low doses (10 or 350 ME) of human interferon-alpha (HIA) were intranasally applied to young (3-4 months) and ageing (12-15 months) Wistar rats during food conditioning. In control groups, development of the conditioned reflex to acoustic stimulus (tone) did not differ significantly in young and ageing rats in the course of chronic applications of the HIA. However, the control ageing rats were better than young rats in time-interval conditioning. Small doses of HIA do not cause anorexia in rats whereas large doses do so. Tone-conditioning did not change in rats of both ages when they were treated with 10 ME of the HIA; moreover, 350 ME increased food motivation, especially in young rats. Time-interval conditioning in aging rats was descended by both doses to the level of young rats, whereas in young rats it did not change at all. We suggest that these differences between ages may by accounted for be different affinity and concentration of micro-opiod receptors (which are the targets for the HIA) in the brain structures responsible for food behaviour, and for counting time intervals.

The roles of various projection areas of the motor cortex in the reorganization of the natural coordination of head and forelimb movements in dogs.

A food-related operant reaction was developed in dogs, in which animals had to maintain tonic elevation of the forelimb to hold a bowl while eating with the head tilted towards the feeder. The acquisition of this reaction involved rearrangement of the natural coordination of head and limb movements which appeared at an early stage of training of the dogs. Forelimb elevation was initially accompanied by anticipatory raising of the head, while lowering of the head led to lowering of the elevated limb. Limb elevation could only be maintained in the posture in which the head was raised. The new coordination required for obtaining food, contrary to the innate coordination and consisting of tonic elevation of the limb with the head lowered, could only be achieved as a result of training. Previous studies have established that lesioning of the primary motor cortex (MI) in the hemisphere contralateral to the working limb leads to stable impairment of the learned coordination, with regression to the initial coordination. The present report describes studies of the effects of local lesions of various projection areas of MI on performance of the learned coordination. Dogs which had acquired the learned operant reaction requiring the new head/limb coordination showed impairment only after lesioning of the representation area of the working limb in the MI; lesioning of the representation area of the head had no such effect.

Recovery of a motor skill in rats with different forelimb preferences after lesioning of the caudate nucleus: the role of intense training.

The aim of the present work was to study the effects of training on the restoration of a lateralized motor skill (a food-procuring forelimb movement) in Wistar rats (n = 83) after lesioning of the caudate nucleus in conditions of infrequent testing and intensive retraining. On the basis of the training results, the rats were divided into those preferring the right (right-handers) or left (left-handers) limb. Testing was followed by lesioning of the head of the caudate nucleus on the side contralateral to the preferred paw. Animals with identical initial preferences were then divided into two groups: an infrequently tested group in which recovery of the skill was tested once weekly for five months, and an intensive retraining group, in which experiments were performed 3-4 times weekly, again for five months. After surgery, animals had to perform the food-procuring skill only with the "impaired" paw. Differences in the recovery of the skill were seen in animals with different limb preferences both in conditions of spontaneous recovery and in those recovering with training. Overall, animals with lesions of the left caudate nucleus (right-handers) showed better recovery than animals with lesions of the right caudate nucleus (left-handers) in both spontaneous recovery and in recovery with training. These findings suggest that the central neural mechanisms of recovery of a lateralized motor skill after unilateral lesioning of the caudate nucleus are different after lesions to the right and left hemispheres.

[Role of the parietal associative cortex in "counting" behavior of dogs].

Influence of the combined and isolated lesions of areas 5 and 7 of the parietal cortex on the counting behavior was studied in experiments with 6 dogs. Instrumental feeding reaction (lifting and placing the forepaw on the foodwell) was established. The positive conditioned stimulus was a series of 5 clicks with variable interclicks intervals and the negative (non-reinforced) conditioned stimulus was a series of 3 clicks, so that asymmetrical differentiation was elaborated. Combined bilateral lesions of areas 5 and 7 and an isolated lesion of area 5 resulted in a severe impairment of the numerical discrimination for two months, whereas the isolated lesion of area 7 did not lead to any problems in differentiation. The conclusion was made that area 5 is critical for numerical discrimination of sequential stimuli.

[Recovery of motor skills after the caudate lesion in rats with the different prefered forelimb: the role of intense retraining].

Rats were trained for instrumental reaching (17 mm) of a sunflower seed from a horizontal tube 12 mm in diameter. After training, rats were divided into groups, "right-" and "left-handers", by the forelimb preference. Unilateral electrolytic lesions of the head of the caudate nucleus contralateral to the prefered forelimb were performed. After surgery, animals were retrained to perform the food-retrieval reaction by the same forelimb (reaching reaction by the "intact" forelimb was prohibited by a special bracelet). Both right- and left-handers were divided into groups of rare and intense retraining. Over the course of five months, animals of the groups of rare training were tested once a week, whereas the intense retraining was performed three or four times a week. Rats with right and left forelimb preference were shown to recover the reaching skill with different rates. In general, animals with left-side caudate lesion (right-handers) recovered the skill better both under condition of spontaneous recovery (rare testing) and intense retraining. The results suggest different mechanism of skill recovery after the right- and left-side brain lesion.

Neuron activity in the anterolateral motor cortex in operant food-acquiring and alcohol-acquiring behavior.

The interactions of the neuronal mechanisms of food-acquiring behavior and newly formed operant alcohol-acquiring behavior were studied by recording the activity of individual neurons in the anterolateral area of the motor cortex in chronically alcoholized rabbits. Adult animals learned food-acquiring behavior in a cage with two feeders and two pedals, in the comers (the food in the feeders was presented after pressing the corresponding pedal). After nine months of chronic alcoholization, the same rabbits learned an alcohol-acquiring behavior in the same experimental cage (gelatin capsules filled with 15% ethanol solution were placed in the feeders instead of food). Analysis of neuron activity showed that the set of neurons involved in supporting food-acquiring and alcohol-acquiring behaviors overlapped, though not completely. These experiments not only help us understand the neuronal mechanisms of the newly formed and the previously formed behaviors, but also facilitate the development of concepts of the similarity of the neuronal mechanisms of long-term memory and long-term modifications of the nervous system, occurring in conditions of repeated intake of addictive substances.

The effects of the quality and probability of reinforcement on feeder selection by lobectomized dogs.

The role of the prefrontal cortex was studied in an active selection situation in which dogs had to choose one of two feeders, with changes in the quality and probability of the reinforcement provided in one of the feeders. The study was performed in two stages. Before surgery, animals were trained to place themselves on a start area during the interstimulus interval. Dogs were presented with a conditioned stimulus for investigation of the sequence of selection of feeders with identical reinforcements. After bilateral extirpation of the prefrontal areas (the proreal gyrus), dogs continuously ran from one feeder to the other during the interstimulus period. In response to the conditioned stimulus, the animals repeated the reaction of selecting the same feeder on many occasions during the first few (7-9) days. When there was a conflict between the probability and quality of reinforcement, the dogs came to prefer the feeder with the greater reinforcement quality despite its lower probability of presentation. In our experiments, operated animals presented with food at probabilities of 30% and 100% performed feeder selections with different probabilities. One of the functions of the prefrontal cortex in intact animals would appear to be to support the reaction of selecting the greater probability of reinforcement.

[Role of different projection areas of the motor cortex in reorganization of the innate head-forelimb coordination in dogs].

Dogs were trained to perform the forelimb tonic flexion in order to lift a cup with meat from a bottom of the foodwell and hold it during eating with the head bent down to the cup. It is known that conditioning of the instrumental reaction is based on reorganization of the innate head-forelimb coordination into the opposite one. In untrained dogs, the forelimb flexion is accompanied by the anticipatory lifting of the head bent down to the foodwell. The following lowering of the head leads to an extension of the flexed forelimb. Tonic forelimb flexion is possible if the head is in the up position. Simultaneous holding of the flexed forelimb and lowered head providing food reinforcement is achieved only by learning. It was shown earlier that the lesion of the motor cortex contralateral to the "working" forelimb led to a prolonged disturbance of the elaborated coordination and reappearance of the innate coordination. In the present work we studied the influence of local lesions of the projection areas in the motor cortex, such as a "working" forelimb area, bilateral representation of the neck, and the medial part of the motor cortex, on the learned instrumental feeding reaction. It was found that only the lesion of the forelimb but not neck projection led to a disturbance of the learned head-forelimb movement coordination.