Monoaminergic mechanisms of the amygdaloid complex actualizing conditioned reflexes of different biological modality]

Microinjection of dopamine and serotonin into the dorso-medial portions of the amygdalic complex of rats increased the latent period of conditioned defense and motor food reactions, spontaneous motor activity, the number of jerks and the value of the conditioned food reflex. Noradrenaline failed to influence the recorded indices of the conditioned food-procuring reflex, but facilitated the conditioned reaction of avoidance, significantly shortening its latent time. The results obtained pointed to the specificity of the neurochemical mechanisms realizing at the level of the amygdalic complex conditioned reflexes of various biological modality in rats.     

Various neurochemical mechanisms for the production of conditioned reflexes of various biologicals modalities at the level of the caudate nucleus]

Microinjection of noradrenaline in to the head of the caudate nucleus failed to influence the latent time of the conditioned reaction of avoidance and the muscle tone, but limited the motor activity and considerably increased the value and the latent time of the food-procuring reflex. Serotonin failed to influence the latent time of the conditioned defence reflex and did not alter the motor activity of rats; however, it shortened the latent period of the conditioned motor-food reflex and markedly stimulated the food-procuring reaction. Dopamine inhibited the conditioned food and defence reflex, but markedly stimulated the spontaneous motor activity of rats. The data obtained pointed to differences in the neurochemical mechanisms realizing the conditioned reflex reactions of different biological modality at the level of the caudate nucleus of rats.     

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.     

Neurochemical mechanisms of the septum in food getting conditioned responses in rats]

The influence of microinjections of monoamines and of glutamic acid into the lateral zone of the septum on a food-procuring conditioned reaction was studied in experiments on rats. Dopamine does not change, while noradrenaline, serotonin and glutamic acid increase the magnitude and number of conditioned food-procuring movements and substantially lengthen the reflex latency. The effects of serotonin are achieved through D-serotonin-, and of noradrenaline, through L-adrenoreactive structures of the neuronal systems of the septum. The influence of glutamic acid on the rat food-procuring conditioned reactions is not linked with the action on the serotonin- or adrenoreactive structures of the septum neuronal systems.     

Monoaminergic influences of the caudate nucleus on conditioned food-getting reactions in rats]

Influence of microinjections of monoamines and glutamic acid into the caudate nucleus head on conditioned food-procuring reaction was studied in experiments on rats. Dopamine, noradrenaline and glutamic acid prolong the latency of the reflex, while serotonin reduces it. However, all the drugs tested reduce the number of conditioned food-procuring movements. The effects of dopamine are achieved through neurone receptors of the caudate nucleus which are sensitive to haloperidol and chlorpromazine; effects of serotonin are mediated through the D-serotoninoreactive systems, and those of noradrenaline, through the alpha-adrenoreactive systems of the neostriatum neurones. The inhibitory effect of glutamic acid is not due to the action on the serotonino-, adreno-, or dopamine receptors of caudate units.     

Role of the lateral hypothalamus and prefrontal cortex in organization of voluntary movements

Roles of the lateral hypothalamus and prefrontal cortex in organization and control of automatized food-procuring movements were studied in rats under conditions of unrestrained behavior with the use of video- and photorecording techniques, destruction of the brain structures, and recording of single neuron impulse responses. The lateral hypothalamus is considered a link in the control system for food-procuring movements, which provides formation of the motor program. The role of the prefrontal cortex is regarded as related to programing and initiation of food-procuring movements and current control of efficiency of their performance. Positions of the lateral hypothalamus and prefrontal cortex within an ensemble of the motor centers, which organizes voluntary movements, are discussed.     

Dynamics of caudate nucleus involvement in the process of internal inhibition of the food-getting reflex]

Changes of slow spindle electrical activity (12 to 14 cps) and evoked potentials in the cat caudate nuclei and the motor cortex were studied at different stages of elaboration of differentiation inhibition of a conditioned food-procuring reflex to acoustic stimuli. It has been shown that participation of the caudate nuclei in the inhibitory process begins at the stage of enhancement of food-procuring activity (second stage) and is apparently due to the animal's strong alimentary motivational excitation. At the third stage the inhibitory influence of caudate nuclei on the animal's motor activity in general, and the activity of the motor cortex in particular, develops to the full.     

The effect of ablation of the caudate nucleus on the alimentary zone of the lateral hypothalamus]

A conditioned food-procuring reaction previously elaborated to an acoustic stimulus was reproduced in chronic experiments on six cats by means of direct electrical stimulation of the posterior parts of the lateral hypothalamus. Folloiwng extensive bilateral electrolytic ablation of the caudate nucleus, conditioned food-procuring reaction to the stimulation of the hypothalamus could not be reproduced for 40 to 70 days. The conditioned foor-procuring reflex to the acoustic stimulus disappeared for 14 to 30 days to be subsequently spontaneously restored. After caudatotomy, a diminution of the average amplitude of background oscillations and of evoked potentials to acoustic stimuli was recorced in the examined zones of the lateral hypothalamus. The part played by the caudate nucleus in the processes of alimentary behaviour activation is discussed.     

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.     

The participation of the parafascicular thalamic nucleus and of the neostriatal cholinoreactive system in regulating the food-procuring reflex in rats at different stages of learning]

Effects of bilateral lesions of the thalamic parafascicular nucleus (Pf) and bilateral microinjections of scopolamine (cholinolytic) and carbacholine (cholinomimetic) into rat neostriatum on the strength of pressing the bar at different stages of acquisition of food-procuring reflex were studied in 51 rats. At the stage of training of food-procuring movements (only strong bar pressings were reinforced) without introduction of a conditioned stimulus, the Pf lesions decreased the rate of learning and increased the number of week pressings. At this stage, scopolamine neostriatal microinjections against the background of the Pf lesions increased the number of strong and did not affect the number of week bar pressings. On the contrary, carbacholine decreased the number of strong and increased the number of week pressings in comparison with the preinjection background. In the trained group of rats, at the stage of reflex restoration (strong bar pressings were reinforced only during the action of a conditioned stimulus) after the Pf destruction, the reflex restoration time depended on the level of presurgery training. Striatal scopolamine injections that primarily after surgery led to a high level of correct reflex realization induced a sharp impairment in reflex performance on a microinjection day, and carbacholine microinjections against the background of low reflex performance did not change this level after surgery.     

Peculiarities of modifying influence of the factors forming the functional status of the central nervous system on dynamics of the rat higher nervous activity disturbances totally exposed to electron and gamma-radiation at a dose of 100 Gy

The dynamics of using a stabilized motor defensive conditioned reflex of active avoidance in "shuttle-box" in rats after the total influence of high energy electrons and gamma-rays at a dose of 100 Gy and a modifying influence of the two most important factors forming the functional status of the central nervous system: the stage of the conditioned reflex consolidation and typological peculiarities of the higher nervous activity have been investigated. The influence of both types of ionizing radiation has been shown to cause far more profound disturbances of non consolidated conditioned reflexes in comparison with the automatized conditioned reflexes and provoke an inverted picture of disturbances in the animals with opposed peculiarities of the higher nervous activity. The qualitative picture of the dynamics of disturbances that are caused by these types of radiation is identical. In summary, the studied conditions that form the functional status of the central nervous system determine the nature of neuroradiation syndrome to a greater extent than differences in the effectiveness of these types of radiation.     

The organization of instrumental food-procuring movements in rats]

The roles of the lateral hypothalamus, basolateral nucleus of the amygdalar complex, the second field of the frontal cortex, and ventromedial thalamic nucleus in organization of the fast ballistic food-procuring movements were studied in albino rats. Sequences of uni- and bilateral destruction of the brain structures were assessed by photorecording. Movement-related neuronal activity in these structures was recorded in freely moving animals. A specific involvement of each of the above listed structures in organization of food-procuring movements was shown. The lateral hypothalamus seems to participate in initiation of the motor program and its efficient realization, the basolateral amygdala appears to produce activatory, training, and stabilizing effects. The second field of the motor cortex leads in movement acquisition (i.e., in memorizing) and decision making about triggering the program. The idea about the relay role of the thalamic motor nucleus is supplemented by understanding of its more complex integrative function.     

Generalization of an instrumental defensive conditioned reflex elaborated to electric stimulation of the hypothalamus in dogs

Generalization of defensive conditioned reflexes elaborated to electrical stimulation of the lateral hypothalamus (LH) was studied in four dogs with electrodes implanted in various structures of the limbic system. Electrocutaneous stimulation was switched off when the dog lifted the foreleg to a definite level. Generalization of the conditioned reflex was manifested in different degrees when testing different formations of the limbic system, or testing one and the same structure, but at different stages of conditioning. Two types of generalization were found: the first one--a well pronounced motor reaction, by its latency, level and duration of lifting the foreleg similar to movements appearing in response to the conditioned stimulus; and the second one--low amplitude or short-term movements differing from conditioned ones. The first type of generalization was observed in response to stimulation of LH, contralateral to the point of signal stimulation, of the ventromedial hypothalamic nucleus, the mammillary bodies and the basal, lateral and to a lesser degree, the central nucleus of the amygdaloid complex; the second type--in response to stimulation of the ventral hippocampus, the medial and lateral septum nuclei.     

Electrical activity of the lateral hypothalamus related to food-procuring movements of rats

On freely moving albino rats we demonstrated that, when fast food-procuring movements are performed, the mass electrical activity of the lateral hypothalamus (LH) is suppressed 1.6–2.0 sec before the movement beginning recorded with a photoelectrical device. Videorecording of the movements and recording of the spike activity of LH units showed that the latter are activated 1.0–0.1 sec before the movement initiation. The LH is considered a motivation-related structure, which serves as a source providing an increase in the excitability of the structures involved in the control of food-procuring movements and, further on, supporting this increased excitability. The LH is also a component of the mechanisms providing formation of the motor program. The role of the LH in the ensemble of motor centers, which organize and control voluntary movements, is discussed.     

Interhemispheric motor asymmetry of conditioned feedback

The interhemispheric asymmetry and lateralization of motor functions, as applied to backward conditioning, was studied in two dogs that afterwards turned to be a right-hander and a left-hander. In the process of food-procuring instrumental conditioning it was revealed that one of the dogs predominantly used the right paw (with the dominance of the left hemisphere) and the second animal used the left paw (the right brain hemisphere dominated). The earliest signs of lateralization of the motor functions were observed in the backward conditioned connections (which had been formed earlier than the direct connections or direct conditioned reflexes). Consequently, the presence and sign of asymmetry can be predicted on the basis of manifestation of the backward connections observed at the early stages of acquisition of food-procuring behavior. The backward connections are strictly specific and have the same lateralization as the direct ones.     

Organization of a program of automatized food-procuring movement in rats

With the use of techniques of video- and photorecording, local destruction of the brain structures, and recording of the spike responses, roles of the suprasegmental brain structures in organization and control of automatized food-procuring movements were studied in rats under conditions of unrestrained behavior. It is shown that there are several neuronal populations in the prefrontal cortex related to programing, initiation, and current control of the efficacy of performance of food-procuring movements. The lateral hypothalamus is considered a motivational structure. It acts as the source providing an increase in the excitability and further support of the excitation level in the structures, which are links of the systems controlling food-procuring movements. The lateral hypothalamus is also involved in a system providing formation and final application of motor programs.     

Effect of Blocking of Calcium Channels on Cognitive Processes and General Motor Activity in Normal and Stressed Rats

In Wistar rats, we studied the effects of injections of a Ca²⁺ channel blocker, verapamil, on realization of a food-procuring operant conditioned reflex, OCR, and general motor activity within intersignal periods in the norm and under conditions of stress-induced disorders. The OPRs and a few behavioral phenomena (immobilization, grooming, research behavior, orientational and locomotor activity, vertical stands, and intersignal limb movements in a manger) were recorded. The acute stress state was induced by intense acoustic stimulation (a loud ringing sound presented in the course of OCR realization). Inhibition of the conditioned reflex activity (immobilization of the animal within an interstimulus period) and weakening of attention to the manger resulted from stress induction. Stress-related behavioral effects evoked by intense auditory stimulation were eliminated against the background of the action of verapamil, while the OCR and motor activity were not inhibited. Verapamil suppressed reactions of fear and anxiety in a dose-dependent manner and promoted concentration of attention; these effects improved the integrative functions and abilities to adequately estimate the signals in a given situation of the OCR performance. Such effects can be based on weakening of stress-related adrenaline release and certain normalization of the state of the cardiovascular systems due to partial blocking of calcium channels.     

Typological characteristics of conditioned reflex learning in monkeys

Three types of conditioned learning dynamics were singled out in males of the rhesus monkeys by the speed of formation of a positive motor instrumental reflex and differentiation. Type I is characterized by the fastest mastering of separate subprograms and of the whole test program of conditioned behaviour, by optimal functional characteristics in the process of learning and by a high adaptivity in new conditions. The most prolonged formation of the conditioned reflexes occurs in monkeys of the III-d type; 50% of them do not master the whole learning program; monkeys with such type of learning dynamics have no adaptation of previously acquired conditioned stereotype to new environmental conditions. Monkeys of the II-nd type of learning dynamics possess intermediate characteristics. A notion is substantiated of interconnection of higher nervous activity properties with typological characteristics of conditioned learning dynamics in monkeys.     

The effect of vasopressin on memory processes in Macaca fascicularis]

The role of vasopressin (arginin-vasopressin) in the regulation of conditioned instrumental food-procuring reactions and different kinds of memory such as delayed reflexes, image, short-, and long-time memory was studied in monkeys. Motor and autonomic effects of vasopressin were assessed. It was found that in monkeys, vasopressin administration differently affected the simple conditioned food-procuring reactions and memory. During functional disorders of the higher nervous activity, vasopressin was more efficient in its action on memory and its restoration. Formation of two types of vasopressin effects on the higher nervous activity in evolution of mammals is discussed.     

Role of Acetylcholine in the Modulation of Activity of Neocortical Neurons in Awake Animals Performing an Instrumental Conditioned Reflex

We studied modulatory effects of the cholinergic system on the activity of sensorimotor cortex neurons related to realization of an instrumental conditioned placing reflex. Experiments were carried out on awake cats; multibarrel glass microelectrodes were used for extracellular recording of impulse activity of neurons in the sensorimotor cortex and iontophoretic application of synaptically active agents within the recording region. The background and reflex-related activity was recorded in the course of realization of conditioned movements, and then changes of spiking induced by applications of the testing substances were examined. Applications of acetylcholine and carbachol resulted in increases in the intensity of impulse reactions of neocortical neurons evoked by presentation of an acoustic signal and in simultaneous shortening of the response latencies. An agonist of muscarinic receptors, pylocarpine, exerted a similar effect on the evoked activity of sensorimotor cortex neurons. Blockers of muscarinic receptors, atropine and scopolamine, vice versa, sharply suppressed impulse reactions of cortical neurons to afferent stimulation and simultaneously increased latencies of these responses. Applications of an agonist of nicotinic receptors, nicotine, was accompanied by suppression of impulse neuronal responses, an increase in the latency of spike reactions to presentation of a sound signal, and a corresponding increase in the latency of a conditioned motor reaction. In contrast, application of an antagonist of nicotinic receptors, tubocurarine, significantly intensified neuronal spike responses and shortened their latency. The mechanisms underlying the effects of antagonists of membrane muscarinic and nicotinic cholinoreceptors and the role of activation of these receptors in the modulation of activity of pyramidal and non-pyramidal neocortical neurons related to realization of the instrumental motor reflex are discussed.