Influence of neurotensin on behavior of rats with lesions in serotonergic neurons

After serotonergic lesion by administration of 5,7-dihydroxytryptamine into the dorsalis raphe nucleus, effects of neurotensin microinjections into the caudate nucleus and substantia nigra on rat behavior were compared. Serotonergic lesions resulted in motivated excitement of rats manifested as an increase in the number of intersignal motor reactions during realization and, particularly, extinction of thirst conditioned reflex. Neurotensin microinjections into the caudate nucleus facilitated extinction of the conditioned reflex both in operated and control rats, but such microinjection into the substantia nigra facilitated this process only in operated animals. Neurotensin did not change conditioned reflex realization in both groups of animals but decreased emotional excitement of rats in the "open field". The behavioral effects of neurotensin in operated rats are connected with normalization of motivational and emotional states of animals and may be explained by recovery of interaction between the dopamine- and serotonergic systems. It is suggested that the mechanisms of this normalizing effects of neurotensin at the levels of the caudate nucleus and substantia nigra are different and are associated preferentially with its action either on dopamine- or serotonergic structures.     

Conditioned reflex analysis of functional connections between the hippocampus and limbic system structures

Instrumental defensive conditioned reflex elaborated in dogs to stimulation of the dorsal and ventral hippocampus, also appeared, due to generalization, in response to stimulation of a number of limbic structures. Two types of changes in the generalization effects (estimated by parameters of motor conditioned reaction) were observed in the course of conditioned reflex stabilization: enhancement (in response to stimulation of the lateral hypothalamus, lateral nucleus of septum, limbic cortex) and weakening toward complete disappearance (in response to stimulation of the medial nucleus of amygdala and medial hypothalamus). Manifestation of the generalization phenomenon from the brain structures, which are not involved initially into conditioned activity, suggests the existence of close functional connections between these structures and the hippocampus.     

Responses of motor cortex neurons of the cat to auditory stimulation and their role in the instrumental food reflex

The responses of motor cortex neurons in the cat to the presentation of a single auditory click and a series of 10 clicks presented with 1,000/sec frequency were studied under conditions of chronic experiments before and after the development of an instrumental food reflex. After reflex development a single presentation of a positive conditioned stimulus (single click) markedly influenced for 7 sec the appearance of instrumental movements. At the same time, the immediate responses of motor cortex neurons to presentation of the conditioned auditory stimulus had no impact on the appearance in the motor cortex of discharges leading to the realization of instrumental movements. Consequently, motor cortex neurons do not require activation from afferent sensory inputs for the generation of such discharges. The immediate neuronal responses to conditioned stimulation did not inhibit the realization of the instrumental reflex. It is proposed that they are associated with the realization of motor function in the unconditioned defensive response evoked by the presentation of an auditory stimulus. The presence or absence of responses to auditory conditioned stimulation was dependent upon the signal meaning of the stimulus, its physical parameters, and the degree of excitability of the animal.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 4, pp. 539–550, July–August, 1985.     

Unitary activity in the cat motor cortex during a conditioned postural adjustment reflex

Unitary activity in the motor cortex (area 4) during a conditioned postural adjustment reflex was investigated in cats. Responses of the overwhelming majority of neurons connected with conditioned-reflex placing movements were activational in type. They consisted of several components and preceded the movements themselves by 50–600 msec. During realization of incorrect responses to presentation of a differential stimulus and of "spontaneous" interstimulus movements, the unitary responses were similar in direction but differed in their lower intensity and, in most cases, they appeared simultaneously with these movements. In the course of extinction both the conditioned-reflex movements and the corresponding unitary responses disappeared simultaneously. The technique of formation of a conditioned postural adjustment reflex suggested in this paper can be used to from natural, well-coordinated forelimb movements in animals in response to conditioned stimulation which are necessary initial components of more complex behavioral motor responses.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 6, pp. 745–753, November–December, 1984.     

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.     

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.     

The behavioral characteristics of rats selected for their learning capacity]

Experiments were conducted in rat strains selected for high (KHA) and low (KLA) levels of the elaboration of conditioned reflex of active avoidance in shuttle box. KHA rats, as compared with the KLA ones, showed considerably higher indices of learning the shuttle avoidance, a greater number of intersignal runs during learning, a higher level of motor activity under open field conditions and its more marked extinction. These data point at the role of both associative and non-associative processes in the formation of active avoidance reflex. During 5 days of reflex training the rats of both strains retained a high level of defecation until the end of the test that pointed at the emotional strain unceasing in spite of the automatization of the reflex.     

Effect of Acute Stress on the Development of Seizures in a Kindling Model in Rats

We studied the effect of acute stress induced by nociceptive stimulation of the limbs on the duration of ECoG epileptiform activity and manifestation of generalized motor convulsive reactions under conditions of a kindling model of epilepsy in rats. Two and four weeks after termination of the kindling procedure, test stimulations of the hippocampus evoked intense attacks of epileptic activity. Short-lasting pain-inducing stimulation (intense electrical stimulation of the limbs) resulted in noticeable limitation of both ECoG and motor behavioral manifestations of epileptic activity determined by the formation of an epileptogenic nidus. The antiepileptic effect of acute stress was limited in time; manifestations of this effect reached their maximum about 3 h after painful stimulation, while about 6 h after such stimulation they became smoothed to a considerable extent.     

Transformation of conditioned responses of the tonic type

A reversal of signal meaning of stimuli signalling experimental situation was performed on dogs with conditioned defensive motor reflexes to clicks: clicks and electro-cutaneous stimulation were stopped, and the animals were started to be given food in the same experimental situation. Reversal of conditioned defensive tonic stimuli to alimentary ones led to a complex of behavioral and electrographic reactions. Isolated click tests showed that signals of experimental situation considerably affect a fully-elaborated defensive motor reflex. At the same time the preparatory role of certain situational elements may be specialized with regard to the components of the conditioned reflex, in particular to the local flexor reaction.     

Effects of food motivation on spike activity of cat somatic cortex neurons

Spike response to unconditioned electrocutaneous stimulation was investigated in cortical neurons of areas 3 and 4 in untrained hungry cats during heightened excitation motivated by food presentation and when at rest. This reinforcement led to changed background activity level, reduced intensity of the initial stages of spike response, and disappearance of late neuronal response. Neuronal response of the same cortical area to a conditioned stimulus (a clicking sound) during reduced food motivation (the animals being sated during the course of the experiment) was also studied under the effects of instrumental feeding reflex. Coordination between the timing of neuronal response and their corresponding movements was discovered from comparing response pattern accompanying the execution of paw-placing (conditioned reflex and intersignal) movements and those recorded at different levels of food-induced excitation, as well as a similarity between these reactions. It was found that the initial stages of neuronal response to a conditioned signal only occurred during contraction of the brachial biceps muscle, while coordination between their timing and that of EMG changes was dependent on the animal's degree of satiation. Findings indicate the possibility of food-induced excitation substantially influencing spike response pattern in somatic cortex neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 6, pp. 725–735, November–December, 1987.     

Characteristics of cortical responses to electrostimulation of the internal geniculate body during formation of a defensive conditioned reflex]

During elaboration of a classical defensive conditioned reflex the dogs exhibited a dependence of the changes in amplitude and configuration of evoked potentials (EP) to electrical stimulation of the medial geniculate body (MGB), a conditioned stimulus, on the nature of effector manifestation of the conditioned reflex: the late components were the most depressed at multiple phasic reactions and not infrequently increased and became complicated at single and short motor reactions as well as at their incidental absence. The primary oscillations, while mostly remaining unchanged, were depressed in the case of conditioned reactions attended with a general motor restlessness. A difference has been revealed during conditioning in the EP changes to electrical stimulation of MGB and to an adequate peripheral stimulation. It has been assumed that EP changes during conditioned activity are determined by the relationship between the levels of tonic and phasic cortical activation.     

Effect of Oxytocin on the Emotional State and Behavior of Rats under Stress Conditions

Oxytocin, a hormone exerting controlling effects on lactation, sexual and maternal behavior, and cyclic organization of sleep and wakefulness, is capable of significantly modulating reactions of the organism to the action of stressogenic stimuli. We studied the effects of injections of synthetic oxytocin on the behavioral phenomena and emotional state of rats during realization of a proconflict test induced by “punishments” (nociceptive electrical stimuli) in the process of drinking after water deprivation. Intraperitoneal injections of oxytocin in a 4.0 μg dose resulted in shortening of the delays of coming of rats to a water dish and also in an increase in the number of drinks of water punished by electrical stimulation, as compared with the corresponding indices in control animals. After oxytocin injections, the intensity of research activity of rats in the open field, in general, increased. After realization of the proconflict test, locomotor and orientational/research activities in animals preliminarily injected with oxytocin were much more intense than those in control rats (in the latter ones, these activities were sharply suppressed). Injections of oxytocin also led to certain normalization of the emotional state; after the proconflict test, negative shifts in this state in control rats were obvious. Therefore, oxytocin appreciably increases the resistivity of the organism against stress.     

Characteristics of the function of the higher portions of the central nervous system of rats subjected to acute hypoxia in the antenatal period]

A reduction of motor activity, and of the orientative reflex, its more rapid extinction in comparison with control were seen in the sexually mature rats which sustained acute hypoxia during the antenatal period. The experimental animals displayed disturbances of the conditioned reflex activity indicating a worse fixation of the temporary association, weakening of the inhibitory process and reduction of the nervous process mobility. Epileptiform convulsions occurred in presentation of "difficult" experimental tasks. There was also noted an increase in convulsioness after the administration of threshold doses of carasol.     

New data on the correlation of the cardiac and motor components of the instrumental conditioned defensive reflex in dogs

Correlation of heart rate (HR) and conditioned motor reaction (CMR) was studied in dogs with conditioned avoidance reflex by the V. P. Petropavlovski? method. An increase of HR was shown in response to presentation of conditioned sound stimulus reaching maximum directly before CMR beginning. Immediately after the beginning of CMR and further against the background of continuous keeping of the paw in the safety zone, CMR greatly decreases. The CMR changes testify to a heavy weakening of classical conditioned reflex of fear as a result of kinesthetic afferentation signalling about successful keeping of the paw in the safety zone.     

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.     

Role of peripheral adrenoreactive structures in the etiology of disorders of the motor components of rat operant behavior during emotional stress

It has been found in experiments on rats trained to avoid electric stimulation of the foots by pressing the pedal that previous immobilization and administration of adrenaline and isoprenaline (but not noradrenaline) disturbs the accuracy of the realization of motor components of operant behavior. The total beta-adrenoblockers (but not phentolamine and cardioselective beta 1-adrenoblockers) given in doses which do not cause any central effects reduced the negative action of emotional stress. It is inferred that activation of beta 2-adrenoreceptors of skeletal muscles is likely to play a role in the genesis of disturbed motor skill under emotional stress.     

Inhibitory influence of supplementary extraneous stimulation upon neuronal responses in the sensorimotor cortex of the cat during a conditioned reflex

Using alert rabbits trained to perform placing movements in response to a sound click, we investigated impulse responses (IR) of neurons of the somatosensory cortex preceding realization of the reflex by 50–150 msec. When a brief extraneous stimulation (light flashes, audible tone, electrical stimulation of a limb) was applied after initiation of the reflex, learned movements with the earlier behavioral parameters (latent periods and duration) were maintained. However, the IR of neurons to the presentation of a conditioned stimulus (CS) was of lesser intensity and arose 50–250 msec later. A constant extraneous stimulation (an audible tone, a forced stream of air upon the muzzle) or a decrease in the intensity of the CS administered to the threshold of hearing resulted in similar changes in the neuronal responses upon the application of the CS, but the parameters of the learned movements were maintained. We suggest that the cause of these changes in neuronal responses is increased exteroceptive attention to extraneous stimulation to additional extraneous stimulation.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 2, pp. 174–181, March–April, 1991.     

Fast ballistic food-procuring movements in rats: Phenomenology and probable controlling mechanisms

Parameters of fast ballistic food-procuring movements were studied in albino rats. With the use of video and photorecording, the number of attempts used by an animal, to get the food globula, duration of the movements, and their phasic structure were analyzed within the whole learning period and certain experimental days. When the motor skill had been formed, programed ballistic components characterized by hard-to-modify parameters and components with a considerable impact of reverse afferentation in their formation and performance were analyzed. The experimental data are interpreted in terms of the expediency of using the operant motor reactions performed by rats getting food from a narrow manger as a model of voluntary motor activity in electrophysiological, behavioral, neurochemical, and morphological studies. The regularities in formation of motor programs, initiation, realization, and control of the movements, and central mechanisms of these phenomena are discussed.     

The retroactive action of paradoxical sleep deprivation and immobilization stress on the mechanisms of memory and passive avoidance in rats

Influence was studied of 48-hours deprivation of paradoxical sleep (DPS) and immobilization stress on conditioned reaction of fear and security--components of passive avoidance conditioned reflex (CRPA), with simultaneous studying of vertical, horizontal activity, grooming reactions and defecations in an illuminated chamber. The obtained results allow to conclude that DPS inhibits reproduction of memory traces of fear reaction but intensifies the process of learning and activity of memory traces of security reaction. Depending on condition of CRPA elaboration, DPS may disturb or, on the contrary, prolong preservation of passive avoidance. It has been found that the immobilization stress does not influence CRPA preservation and does not weaken the reaction of fear but increases the horizontal activity. It is suggested that the observed changes in behaviour and trace processes are connected with disturbance of sensory informational homeostasis of the nervous system at DPS.     

Activity of neurons in the pedunculopontine nucleus during defensive instrumental conditioning

The activity of 109 neurons in the compact and diffuse parts of the pedunculopontine tegmental nucleus (PPTg) was recorded in freely moving rabbits during the acquisition and actualization of the defensive instrumental conditioned reflex. It was found that 47% of the recorded neurons responded to a conditioned stimulus (CS). This finding suggests the involvement of the PPTg in the instrumental conditioning. A significant prevalence of the excitatory conditioned responses to the CS suggests the predominantly activating influence of the PPTg on its projection structures during conditioning. The neuronal responses to the CS were classified into several basic patterns reflecting stimulus effects, the structure of the behavioral act, and the nature of the reinforcement. They indicated the involvement of the PPTg in attention, motor learning, and reinforcement. A significant decrease in the reactivity of the CS of the PPTg neurons as a result of learning specialization was shown. The revealed differences in the associative and reactive properties (with respect to CS) between the neurons of the compact and diffuse PPTg parts testify to the functional heterogeneity of this structure and suggest the leading role of the cholinergic compact part of the PPTg in the instrumental defensive conditioning. Thus, the obtained evidence suggests the involvement of the PPTg in the mechanisms of attention and acquisition of the active defensive motor conditioning.