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.     

Conditioned reactions to time of hypothalamic neurons. The perifornical nucleus]

In 40% of the 52 neurones of the hypothalamic perifornical nucleus in alert rabbits conditioned trace reactions of the activational (52%) and inhibitory (48%) type were recorded in the course of elaboration of a conditioned motor reflex to time. The sign and pattern of the trace responses were determined by the nature of cell reactions to actual paired stimuli. After 50 to 70 pairings, the unit trace conditioned reaction to time persisted for a period of 10 to 15 successive omissions. Trace responses were observed most frequently in the 5th of 8th omissions. In some cases conditioned enhancement of cell activity coincided with the conditioned motor response to time. This fact together with the maximal development of a summery trace cellular response at the moment of formation of conditioned motor reactions attests the participation of neurones of the perifornical nucleus in maintaining conditioned motor activity.     

Conditioned responses to time of hypothalamic neurons. The ventromedial nucleus]

Conditioned reactions to the time of regularly (every 30 sec.) presented pairings of an acoustic and an electrical cutaneous stimuli were studied in neurones of the hypothalamic ventromedial nucleus in an alert rabbit. Conditioned reactions of an inhibitory (81%) and activating (19%) types were elaborated in 27 out of 63 units (43%). They were significantly reproduced at six to nine omissions of stimulations at the stage of the 50th to 70th pairings. The maximum manifestation of trace processes coincides with the initial formation of a vegetative (electrocardiogram) component of the behavioral conditioned reflex to time. Significant correlation has been shown between the frequency of spikes in the pairings and their omissions, and the corresponding changes in heart rate at the same temporal intervals. This testifies to the involvement of the ventromedial nucleus structures in the formation of the vegetative component of the behavioral conditioned reflex to time. Common characteristics and peculiarities of conditioned reactions to time have been revealed in units of the hypothalamic ventromedial and perifornical nuclei in accordance with morpho-functional properties of the examined structures.     

Effect of dalargin on the processes of memory and learning in the rat

In experiments on rats, the influence was studied of dalargin on the elaboration and preservation of various homogeneous and heterogeneous conditioned reflexes (CRs) elaborated in single and multiple pairings. The effect of dalargin on the processes of learning and memory was compared with the action of the peptide on the activity of hypothalamic neurones. Administration of dalargin delayed the elaboration of maze defensive CRs and practically did not affect the elaboration of two-way avoidance. The preservation of CR also deteriorated under the influence of dalargin. Administration of dalargin 10 min before the CRs testing did not prevent their reproduction. When using CRs elaborated in a single pairing, dalargin disturbed the preservation of the drinking CR and improved that of passive avoidance CR. Dalargin in this dose affected the emotional state of animals in the open field and did not significantly affect their motor activity. Dalargin suppressed impulse activity in 17 out of 22 tested neurones of the lateral hypothalamus, with maximum effect in 20-50 min after its administration. The obtained data show that the character of dalargin action on the elaboration of CR and mainly on its consolidation, depends on the character of the elaborated CR and is probably due to great extent to the effect of the peptide on the brain emotional mechanisms.     

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.     

Dynamics of the activity of rabbit visual cortex neurons during elaboration of elementary conditioned reflexes to time and association

Elaboration of a reflex to time (with omissions of stimuli) and of association; light--light + electrocutaneous stimulation of the paw was studied on neurones of the rabbit visual cortex. It was shown that by similarity of patterns of the discharge to a conditioned stimulus and to reinforcement, 83% of neurones reveal the formation of a reflex to time, and 57%--elaboration of association. Three ways of coding plastic reorganizations of the neuronal discharges are suggested; by the total number of spikes in the response, by the total sum of inhibitory periods, and by the pattern of the response. It has been found that in the reflex to time the early components of the response to the stimulus are reproduced during omissions; in elaboration of the association the late components of the discharge reaction to reinforcement are mainly repeated. Most cells with plastic reorganizations possessed polysensority and revealed discharge sensitization during habituation.     

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.     

The reflection of the operations of comparing afferent flow with internal pretuning in the neuronal impulse activity of the frontal cortex in the dog

From 192 neurons, recorded in the frontal cortex of dogs trained for differential classical conditioning of salivary reflex, 24 cells were identified related to the detection of matching-mismatching conditioned and unconditioned stimuli (CS and US) to internal set. Impulse reactions of the 1-st group of neurones (11 cells) to US disappeared, when any deviation from standard pattern of CS-US pairing occurred or when US characteristics were suddenly changed. These reactions developed again at the 3-5th repeated presentation of the stimuli delivered in "new" regime. Neurones of the 2-nd group (13 cells) were activated in response to CS only when two sequential CSs had different meaning. The 1-st group of neurones is considered as detectors of matching, and the 2-nd group--as detectors of mismatching the stimulus to its neural model, formed by mechanism of reinforcement.     

Reflection of the process of conditioned reflex formation in shifts of the steady potential level]

In chronic experiments on rabbits with non-polarizable electrodes shifts of steady potential level (SPL) are recorded from the brain surface during extinction of the orienting reaction and formation of a conditioned defensive reflex. During each of these processes they have their typical parameters and are respectively denoted by the author as: orienting (appearing in response to a new stimulus), conditioned (to a signal atimulus), unconditioned (to an electro-cutaneous stimulus) and trace SPL shifts (developing after stimuli pairing). Trace shifts are the earliest SPL shifts originating as a result of pairing. They are manifested more regularly, than conditioned ones, considerably exceed them in amplitude, may differ from them in their sign and reach maximum values in a few seconds after the pairing. It has been assumed that formation of conditioned temporal connections depends above all on the appearance of a new kind of activity, resulting from pairings and reflected in the SPL trace shifts. This activity possibly constitutes the neurodynamic and metabolic processes underlying memory consolidation.     

Sensitization and habituation of command neurons during a defensive reflex in grape snails

All investigated neurones were classified into functional groups depending on their participation in unconditioned avoidance reflex of pneumostome closure. Habituation was produced by tactile stimuli applied with a frequency of 0.1 c/s. Spike responses of neurons participating in processing sensory information habituated gradually, while reactions of command neurones of avoidance behaviour became sensitized to the second or third stimulus of the series. Behavioral reaction was sensitized in parallel with command neurones in spite of habituation in other types of nerve cells. A conclusion is drawn that behavioral habituation is due to waning of responses in all the participating neurones, but the independnet process of sensitization is due to sensitization of command neurones. Probable mechanisms of neuronal sensitization are discussed.     

Correlation of neuronal reactions of different regions of the neocortex of the rabbit to conditioned positive and inhibitory stimuli

The activity of neurones of the visual and sensorimotor areas of the neocortex was simultaneously recorded in rabbits under the action of conditioned, inhibitory stimuli (CS, IS) and at simultaneous presentation of CS and the unconditioned stimulus (US) after trans-switching of the positive and inhibitory conditioned reflexes. Mean time of conjugated reactions of simultaneously recorded pairs of neurons is similar under the action of CS, combined action of CS and US and under IS. During the IS action as compared with CS, the phasic activity of some neurones in different areas increased, and due to this the similarity of reactions also increased; in other pairs of neurones the reactions weakened and the responses similarity decreased. The frequency of the appearance of intervals of the conjugated excitation after CS corresponds to 4.3 Hz; under combined action of CS and US it increases up to 5.9 Hz, and after IS--it decreases to 3.6 Hz. The order of coming into conjugated action of different pairs of neurones changes depending on the signal significance of the stimuli.     

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.     

Interaction of brain macrostructures during organization of behavior

The data on anatomical connections, injury consequences, summate and unit activity records may be represented as a chain of events running in sequence and in parallel in the brain of higher mammals. Internal (metabolism) and external (odour, pain, etc.) incentive unconditioned stimuli activate motivational structures of the hypothalamus, which in turn activates the frontal areas of the neocortex and the hippocampus. In case of coincidence of earlier neutral external stimuli with the action of reinforcing unconditioned ones, the hippocampus becomes the first place of convergence of combined afferentiations. After formation of the act, those external stimuli or their engrams which have been accompanied earlier by satisfaction of a certain need, are selected as a result of joint action of the hippocampus and the frontal cortex. By comparison of motivational excitation with available stimuli or their engrams retrieved from memory with the participation of the temporal cortex, an emotional colouring of the stimuli and engrams is formed in the amygdala leading to isolation of a dominant motivation, destined to be satisfied in the first instance. The program formed in the frontal cortex, comes to the basal ganglia where, by means of interaction with the parietal cortex, it confirms to the spatial coordinates of the forthcoming action. From the fronto-striate system, the excitation comes through the motor cortex to the effector organs accomplishing the behavioural act.     

Trace reactions following combination of a sensory stimulus with polarization of the visual region of the cortex]

Spontaneous activity and responses to photic flashes and tones of 133 neurones were recorded in the visual cortex during polarization of the same area (1.5 to 10 muA, 5 to 30 min) and after it (one to 52 min). Responses of cells to two unimodal stimuli of different parameters were analysed, of which one was presented repeatedly during the polarization ("positive"), and the other one to three times ("negative"). Depending on the previous "learning", 47.4% of the units responded after the polarization to "positive" photic stimulus and 37,8%--to acoustic stimulus. The trace effects of the stimuli pairings are reproduced in polarization after-effect by the action of the sensory signal alone. The recorded differences in the nature and duration of the reproduction of trace processes formed to an adequate and inadequate stimuli, are due to the dissimilar action of polarizing currents on neurones of the cortex cross-section and to different effectivity of the visual and non-visual influences related to it.     

Naloxone antagonism of conditioned hyperthermia: an evidence for release of endogenous opioid.

Morphine-induced hyperthermia was conditioned to environmental stimuli by pairing each injection (10 mg/kg) with the smell of anise oil. After 39 pairings the smell itself acquired a conditional property of eliciting hyperthermia which was antagonized by naloxone.     

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.     

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.     

Several mechanisms of acetylcholine participation in the processes of formation and fixation of temporary connections

Microphoretic application of acetylcholine (ACH) to the neurones of the rabbit sensorimotor cortex elicits changes of spontaneous and evoked activity which do not correlate with one another and which persist up to two minutes after the end of ACH application. Following the formation of a defensive conditioned reflex to sound, the reactions to ACH in units involved in the formation of the temporary connection are intensified as compared with their reactions before conditioning and with reactions of those neurones which did not elaborate a temporary connection. The possible mechanisms of ACH participation in the processes of elaboration and fixation of temporary connections are discussed.     

The effects of neuroleptics and nialamide on defensive conditoned reflex in rats.

Experiments were carried out on male Wistar rats after development of defensive conditioned relex during 6 weeks of training. In one series of experiments chlorpromazine, haloperidol, pimozide or fluspirilene were used in doses of 0.05, 0.5 and 5.0 mg/kg intraperitoneally. In another series of experiments nialamide was given intraperitoneally in a dose of 140 mg/kg 16--18 hours before administration of one of these neuroleptics. A delay in the time of appearance of the defensive conditioned refex was observed after administration of neuroleptics in all animals. In some rats neuroleptics caused complete disappearance of the conditioned refex as well as the defensive unconditioned refex. Previous inhibition of monoamine oxidase activity obtained with nialamide increased evidently the inhibitory effect of the studied neuroleptics on the appearance of defensive conditioned reflex.     

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.