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.     

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.     

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.     

Effect of GABA on a temporary connection in a neuronal population of the sensorimotor cortex in rabbits

Evoked activity of sensorimotor cortical neurones in response to stimulation of the pyramidal tract, medial lemniscus and reticular nucleus of the midbrain tegmentum; driving reaction of cortical neurones at stimulation of these brain structures of growing frequency, and conditioned reflexes elaborated by combination of direct stimulation of the sensorimotor cortex and electrocutaneous stimulation were studied in awake nonimmobilized rabbits. Application to the cortex of GABA solutions of low concentration (less than or equal to 1%) emphasizes the evoked neuronal responses, facilitates the appearance of driving reaction and contributes to the manifestation of the temporary connection. Application of GABA solutions of higher concentration (greater than 2%) leads to opposite effects. Positive correlation is found between electrical and behavioural phenomena. The described experimental approach may be used for analysis of various types of influences on temporary connection formation.     

Organization of the connections of the putamen with the cerebral cortex and hypothalamus]

Connection between the putamen, the brain cortex and the hypothalamus, as well as the role of the former in different aspects of purposive behaviour have been studied in a complex morpho-physiological investigation. In 12 cats, after developing a symmetrical active-defensive conditioned reflex, unilateral electrolysis of the putamen has been performed and the number of conditioned-reflexive reactions have been counted before and after coagulation. The brains have been treated after Nauta--Gygax, Fink--Heimer with additional staining after Kawamura--Niimi. Monosynaptic connections of the putamen with frontal, precentral, postcentral, orbital, parietal cortical areas have been revealed; direct pathways from the putamen to the infundibulum of the grey tuber, to the posterior and lateral hypothalamic nucleus have been demonstrated; participation of the putamen in the formation of active-defensive conditioned reflexes has been stated, as well as in emotional behaviour with a preferable use either the right or the left foreleg.     

Changes in the cholinosensitivity of sensomotor cortex neurons during conditioned reflex extinction]

Characteristics of neuronal responses of the sensorimotor cortex to ionophoretically administered neuromediators (acetylcholine, L-glutamate) were studied in rabbit in the course of extinction of conditioned defensive reflex. In the majority of neurones the extinction of the conditioned reflex is accompanied by a drop of cholinosensitivity. In a number of neurones the extinction of reflexes either does not change the reaction to acetylcholine, or enhances it. The analysis of these reactions permits to assume the existence of a group of neurones directly involved in the formation, fixation and storage of the temporary connection.     

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.     

The modulation of the pulse activity of neocortical neurons during a conditioned reflex]

Spontaneous and evoked activity of neurons in the sensorimotor cortex was recorded in cats with learned conditioned placing reaction before, during, and after the iontophoretic application of synaptically active substances. It was shown that apart from direct excitatory effect on the cortical neurons during its application, glutamate (Glu) exerted some modulatory influence on unit activity in subsequent 20 min. Noradrenaline suppressed the background and evoked activity through beta 1 adrenoreceptors. Activation of beta 2 adrenoreceptors by metaproterenol was accompanied by facilitation of the background and evoked activity during application and 10-20 min after. The joint application of Glu and metaproterenol improved facilitation of neuronal responses evoked by conditioned stimuli. Application of levodopa, like Glu, increased the background and evoked activity of many sensorimotor cortical neurons. The joint effect of Glu and levodopa was not substantially more intensive than the changes produced by the isolated application of any of these substances. A nonselective blocker of DA1 and DA2 receptors haloperidol either increased or did not change the background and evoked activity of some cortical neurons. In contrast to isolated application of Glu, simultaneous application of Glu and haloperidol to neocortex suppressed the neuronal responses associated with conditioned movements. The results suggest that the Glu-induced potentiation is substantially realized through molecular mechanisms common for Glu and dopamine, probably, through Gi-proteins. The conclusion is drawn that the adrenergic and dopaminergic inputs to neocortical neurons are involved in the Glu-mediated plastic changes in the cortex during conditioning.     

Conditioned alimentary motor reflexes in cats following destruction of the scorpula]

Bilateral ablation of the putamen results in temporary disappearance of natural as well as artificial conditioned motor reflexes in cats. Further training is necessary for their reestablishment. Restored conditioned reflexes appear with a long latency. After partial bilateral ablation of the putamen, animals that have been trained not only to press a pedal, but also to make a choice between a right or left feeding tray, lose the latter ability. After the reestablishment of conditioned reflexes, the animal makes a correct choice of side only in 68--70% of cases. After total bilateral ablation of the putamen the animals lose artificial conditioned reflexes. The results suggest that the putamen has a close relation to the mechanisms of learning and memory.     

Effects of selective blockade of synaptic transmission in the parafascicular complex on activity of sensorimotor cortex neurons

Neuronal firing activity pattern in the sensorimotor complex and conditioned reflexes produced by blockade of noradrenergic and serotoninergic input to the parafascicular complex (CM-PF) were investigated during chronic experiments on cats in which lever-pressing reflex had previously been set up. Micro-injection of obsidan, a beta-adrenergic blocker and lysergide, a serotonin blocker, were found to produce intensification and inhibition, respectively, of neuronal spontaneous firing activity in the sensorimotor cortex, with both blockers having a similar (inhibitory) effect on neuronal response induced by conditioned acoustic stimuli. Blockade of monoaminergic inputs to the CM-PF temporarily suppressed execution of the conditioned reflex and the non-conditioned reflex of lever-pressing (for 30–60 min). The study concludes that the pattern of effect produced by the monoaminergic system on the sensorimotor cortex is largely determined by indirect as well as direct agents and that such effects are mediated by neurons belonging to the CM-PF complex of the thalamic nuclei.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 22, No. 3, pp. 327–336, May–June, 1990.     

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.     

Participation of GABA-ergic structures in producing the effects of haloperidol

A study was made of the effect of haloperidol on convulsions induced in mice by bicuculline and thiosemicarbazide and on the recovery cycles of the primary response in the rat sensorimotor cortex. In doses of 0.3--0.5 mg/kg producing a tranquilizing effect, haloperidol exerts a protective action in convulsions induced by bicuculline blocking of the GABA receptors and enhances the depression of the testing response during recovery cycle of the rat sensorimotor cortex primary response. It means that over this dosage range haloperidol potentiates GABA-induced effects. An increase in the neuroleptic dose up to 1--2 mg/kg entails disappearance of the efficacy shown by both the tests. The authors' own and reported data suggest an important role played by the postsynaptic GABA-positive effect in realization of the tranquilizing action of haloperidol and other neurotropic agents.     

The effect of acetylcholine and atropine on the temporal connection in the neuronal populations of the motor cortex]

On alert non-immobilized rabbits the activity of neurones in the sensorimotor cortex was studied at pair combination of brain structures stimulations. During omission of the reinforcing stimulus at the place of its expected presentation a complicated complex develops of neurones impulses reconstructions, consisting in reproduction of responses and activity changes which by their configuration differ from them and usually appear in later terms. Direct acetylcholine application on the cortex promotes manifestation of both types of neurones activity reconstructions. But atropine application depresses mainly the second type of reconstructions. Besides, acetylcholine increases the general duration of the given conditioned effects, but atropine decreases it.     

Effect of activating the putamen on alimentary conditioned reflexes in dogs

The influence was studied of the near-threshold high- and low-frequency stimulation of the putamen on achievement of alimentary conditioned reflexes in dogs. Both low- and high-frequency activation of the examined structure significantly changes the parameters of intermediate secretion, of the salivary conditioned reflexes, without influencing unconditioned ones. Unilateral stimulation disturbs the achievement of positive and inhibitory conditioned reflexes to a greater extent than bilateral one. Difference between the effects of low- and high-frequency stimulation has been revealed.     

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.     

Effect of strychnine on the neuronal reactivity of the sensorimotor cortex and the temporary connection in rabbits

On awake nonimmobilized rabbits, evoked activity was studied of the sensorimotor cortex neurons in response to stimulation of the pyramidal tract, medial lemniscus and reticular nucleus of the midbrain tegmentum by stimuli of different frequencies, and driving reaction of cortical neurons to stimulation of these brain structures by series of stimuli of increasing frequency. Conditioned reflexes were also studied, established on the basis of combination of direct stimulation of the sensorimotor cortex and electrocutaneous stimulation. Application of the cortex of low concentration of strychnine solutions (less than 1%) heightened neurons reactivity and provides for the formation of temporary connection. Application of strychnine solutions of higher concentration (greater than 1%) led to opposite effects. Interconnection of electrical and behavioural effects is discussed.     

Conditioned-reflex food selection in mongrel white rats exposed to high temperature]

Under condition of normal temperature the conditioned reflectory runnings of rats on the audible irritants were developed more quickly during dry food than damp one. Daily influence of high temperature during two hours and partially water deprivation resulted in reduction of the conditioned reflex which had been developed before during dry food. The reproduction of the conditioned reflexes during dry food failed. The essential changings in the conditioned reflexes during damp and dry food were not found when animals had become overheating without restriction of water consumption. During daily heat affecting at the end of the second week animals adapted to high temperature. This statement is confirmed by lowering the rectal temperature, decrease of the breath rate, daily water consumption and restoration of the activity of conditioned reflexes.     

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.     

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.