Integration of conditioned reflex systems in intact and callosotomized dogs

Characteristics of integrative activity were studied by Kupalov's method of situational conditioned reflexes in 2 groups of dogs with complete section of the callosal body and in group of intact animals. The dogs of the first group were callosotomized before the formation of the conditioned reflex systems, the dogs of the second group--after their stabilization. The level of the reflex systems integration in the first group was considerably lower than in the second one. This testifies to a special role of the callosal body in the initial period of formation of complex conditioned systems. The callosotomized dogs developed inertia of nervous processes which was manifested in slowing down of formation and of adaptive realization of reactions during integration of various reflex systems. It was shown that the integrative activity is provided for by the interaction of cerebral hemispheres at different structural levels.     

On the methods employed to record and measure the human soleus H-reflex

The aim of this study was to investigate if the magnitude of the soleus H-reflex is different depending on the method employed to measure its size (peak-to-peak amplitude vs. area). In this study, 13 healthy human subjects participated, while the soleus H-reflex was induced via conventional methods. In the first experiment, the soleus H-reflex was recorded via two monopolar electrodes and was evoked at least at eight different stimulation intensities in respect to the recovery curve of the H-reflex and at three different inter-stimulus intervals (ISIs) (8, 5, and 2 s). The ISI refers to the time delay between the single pulses delivered to the posterior tibial nerve within a single trial. In the second experiment, the effects of common peroneal nerve (CPN) stimulation at short (2-4 ms) and at long (60-120 ms) conditioning test (C-T) intervals on the soleus H-reflex elicited every 5 s were established. Control and conditioned reflexes were recorded via a single differential bipolar electrode. In both experiments, H-reflexes were quantified by measuring their size as peak-to-peak amplitude and as area under the full-wave rectified waveform. The reflex responses recorded through two monopolar electrodes across stimulation intensities and ISIs measured as peak-to-peak amplitude had larger values than measured as area. In contrast, the magnitude of the reflexes, conditioned by CPN stimulation at either short or long C-T intervals and recorded via a single differential electrode, were not significantly different when measured as peak-to-peak amplitude or as area. Our findings indicate that monopolar recordings yield different reflex sizes depending on the method employed to measure the reflex size, and that the H-reflex measured as area might detect better the homosynaptic reflex depression. The lack of observing such differences with bipolar recordings might be related to changes of the reflex shape at a given stimulus intensity due to inhibitory inputs. The implications of our findings are discussed in respect to human reflex studies.     

On the methods employed to record and measure the human soleus H-reflex

The aim of this study was to investigate if the magnitude of the soleus H-reflex is different depending on the method employed to measure its size (peak-to-peak amplitude vs. area). In this study, 13 healthy human subjects participated, while the soleus H-reflex was induced via conventional methods. In the first experiment, the soleus H-reflex was recorded via two monopolar electrodes and was evoked at least at eight different stimulation intensities in respect to the recovery curve of the H-reflex and at three different inter-stimulus intervals (ISIs) (8, 5, and 2?s). The ISI refers to the time delay between the single pulses delivered to the posterior tibial nerve within a single trial. In the second experiment, the effects of common peroneal nerve (CPN) stimulation at short (2–4?ms) and at long (60–120?ms) conditioning test (C-T) intervals on the soleus H-reflex elicited every 5?s were established. Control and conditioned reflexes were recorded via a single differential bipolar electrode. In both experiments, H-reflexes were quantified by measuring their size as peak-to-peak amplitude and as area under the full-wave rectified waveform. The reflex responses recorded through two monopolar electrodes across stimulation intensities and ISIs measured as peak-to-peak amplitude had larger values than measured as area. In contrast, the magnitude of the reflexes, conditioned by CPN stimulation at either short or long C-T intervals and recorded via a single differential electrode, were not significantly different when measured as peak-to-peak amplitude or as area. Our findings indicate that monopolar recordings yield different reflex sizes depending on the method employed to measure the reflex size, and that the H-reflex measured as area might detect better the homosynaptic reflex depression. The lack of observing such differences with bipolar recordings might be related to changes of the reflex shape at a given stimulus intensity due to inhibitory inputs. The implications of our findings are discussed in respect to human reflex studies.     

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.     

Effect of ablation of the septum pellucidum on the marking of time intervals

It is shown that preliminary ablation of the septum lucidum (the rat group II) leads to a considerable (up to 1000 presentations) and prolonged (up to one year) worsening of the elaboration of time intervals estimation, as compared to intact animals and does not significantly influence the conditioned reflexes to time stabilized before the operation (the rat group I). The great worsening of time intervals estimation is due to disturbance of the very mechanism of the reflex to time. Differences are discussed between the two groups of the operated rats. The septum ablation does not affect the state of conditioned reflexes to present stimuli. In the greater part of the postoperative rats a lowering of alimentary motivation is observed that may be secondarily accompanied by a disturbance of time intervals estimation.     

The role of trace excitatory processes in the formation of conditioned reflexes to time]

I. P. Pavlov's hypothesis on the role of trace excitation in conditioning to time was verified by mathematical methods proceeding from experimental data on elaborating in rabbits a motor alimentary conditioned reflex to a four-minute interval of time. A connection has been established between the experimental characteristics of formation of a reflex to time and some parameters of the presumed dynamics of trace excitation. The analysis helped to establish the shortest and longest intervals to which a reflex to time can be elaborated by the mechanism of trace reflex, as well as the optimal interval to which it is elaborated more easily. The experimental results so obtained are a significant corroboration to the correctness of the Pavlov hypothesis.     

Effect of acute melipramine administration on motor activity and defensive conditioned reflexes of passive and active avoidance in rats

The administration of threecyclic antidepressant melipramine to Wistar rats (15 mg/kg, intraperitonaly, 2 h before of experiments) increases time of an "open field" centre leaving. Thus melipramine does not influence horizontal and vertical activity, and also the number of bolus. At the development of a passive avoidance conditioned reflex melipramine significantly slows down realization of a unconditional mink reflex by untrained rats, increasing the latency of call in a dark compartment of the chamber. After training significant deterioration of a reflex reproduction is observed. At research of a defensive conditioned reflex of active avoidance melipramine worsens both development and reproduction of a reflex. The comparative analysis of the literary data of imipramine action on uptake of serotonine and noradrenaline and the analysis of the literary data on a role of these systems in the processes of learning and memory allows to suggest, that the effect of melipramine is connected mainly to amplification activity of serotoninergic system of a brain. It is supposed, that acute administration of melipramine creates emotionally negative state, worsens processes of learning and memory, strengthening mainly activity of a brain serotoninergic system. It specifies that serotoninergic system of a brain is system of punishment. Its activation interferes with formation and consolidation of connections between conditional and unconditional irritation.     

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 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.     

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.     

Recognition of chemical stimuli by guppy, Poecilia reticulata Peters

An alimentary conditioned reflex to beta-phenylethanol and a subsequent differentiation of cumarine were elaborated in conditions of simultaneous paired choice in guppies. It was shown that beta-phenylethanol in a concentration not over 7 X 10(-6) M is perceived through olfaction. The conditioned reflex persists for a long time: twenty five to fifty days after section of the olfactory nerves (the conditioned reflex is restored after their regeneration) and at least seventy days in intact fishes.     

Neurophysiologic analysis of the critical period of delay of a reinforcing stimulus in the dog

At interval of less than 100 ms between indifferent sound and unconditioned electrocutaneous stimulation, classical defensive conditioned reflex is not elaborated in dogs, in full correspondence with literature data. But intracortical temporary connection is established; this fact is shown by electrographic phenomena, the most specific and demonstrative among them is "conditioned evoked potential". The absence of behavioural (peripheral) and presence of electrographic (central) manifestations allow to assume that for the formation of the conditioned reflex of full value the involvement is necessary of additional activational (motivational) mechanisms, connected with reticular and (or) limbic subcortical structures which do not react to the conditioned stimulus at time deficit in conditions of microdelay.     

Changes in evoked potentials during differentiation inhibition

Evoked responses (EPs) of the auditory and the sensorimotor cortical areas were studied in experiments on cats during formation of a positive food-procuring conditioned reflex to a rhythmic sequence of clicks and during formation of the differentiation inhibition in response to the clicks of the same parameters, but with different frequency. In the positive conditioned reflex the EPs amplitude in the sensorimotor cortex increases; they are enriched by late components and in their general configuration they become much similar to EPs in the auditory area. The EPs patterns both in the auditory and in the sensorimotor areas considerably change in response to the differentiation stimulus, but differently in each of the sites.     

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.     

Interhemispheric asymmetry in rats differentiating figures by size

Motor alimentary conditioned reflex was elaborated in Wistar line rats to presentation of various pairs of figures, those of larger area serving as positive signals. In tests on animals with intact brain and with unilateral hemispheric cortical inactivation, new pairs of figures were used besides basic stimuli. The level of analysis in testing experiment was lower than normal: by 5.6% at intact brain, by 16.4%--at right hemisphere inactivation, by 36.4%--at left hemisphere inactivation. Elimination of the left hemisphere produced prolongation of the conditioned reaction time, signs of frustration and aftereffect. In conditions of right hemisphere inactivation the level of discrimination of figures depended on their specific properties and the side of presentation. Conclusion is made on dominating role of the left hemisphere in analysis of abstract and concrete characteristics of visual stimuli, in control of temporal, spatial and emotional characteristics of reactions in situations when considerable abstraction and distinguishing of generalizing invariant sign "more-less" is necessary for elaboration of the conditioned reflex.     

Conjugation of unit activity in the visual and sensomotor areas of the rabbit neocortex during a conditioned reflex to sound and light

Conjugation of unit activity in the visual and sensorimotor neocortical areas was studied by means of histograms of cross- and autocorrelation in rabbits with conditioned reflex to light (1st group) and sound (2nd group). Relative number of neurones pairs acting in correlation in the areas remote from each other, in intersignal intervals both before and after stimuli did not differ in the 1st and 2nd groups. At the same time delays in neuronal discharges in one area after the other were different. In the 1st group animals there was a predominance of the number of visual area neurones discharging after sensorimotor with a delay up to 125 ms, in comparison with the number of sensorimotor area neurones discharging after the visual one. In the 2nd group rabbits the number of visual area neurones with such a delay of discharges after sensorimotor was less and, on the contrary, a predominance of sensorimotor area neurones was observed discharging after the visual one. The obtained results allow to suggest that neurones of the visual and sensorimotor neocortex areas form a single functional system in cases when conditioned and unconditioned stimuli are addressed to these areas and when only one of the studied areas is the projection zone for the combined stimuli. Organization of the neurones activity in systems in these two cases is different.     

Temporal changes in conscious and unconscious trace phenomena in six to seven-year-old children]

Development in time of unconscious trace reactions as well as a change in the time of reproduction of verbal material in natural conditions was studied by the conditioned reflex to time method on 107 school children aged from six to seven years and on 35 subjects of the same age from a kindergarten. It has been found that in schoolchildren the transfer of trace reactions to long-term storage is completed faster, and their voluntary acts in the course of conscious reproduction of an interstimuli intervals are more adequate than in the kindergarten children of the same age. The trace phenomena formed in natural conditions and in the laboratory experiment develop in time in a similar way. The change in time of conscious trace phenomena is of a more complex nature than of the unconscious phenomena. The practical significance of the data obtained is noted.     

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.     

Female rats develop conditioned place preferences for sex at their preferred interval

Female rats engage in approach and avoidance behaviors directed toward the male to "pace" the rate of copulation. These pacing behaviors result in a pattern of vaginocervical stimulation that triggers a neuroendocrine reflex that is important for pregnancy to result from insemination. Each female rat has a preferred pacing interval, and females develop conditioned place preferences for paced sex versus nonpaced sex. Research from this laboratory has reported that extracellular dopamine concentrations in striatum and nucleus accumbens are greater in female rats that are engaging in paced sex compared with those engaging in nonpaced sex. Furthermore, females who have males removed at their preferred intervals during a copulatory bout show extracellular dopamine concentrations comparable to females engaging in paced sex. It is unclear, however, whether they would also develop a conditioned place preference for sex under such conditions. This experiment was designed to address this question. Female rats had six exposures each to a chamber in which they engaged in nonpaced sex and a chamber in which they engaged in paced or preferred pacing interval sex. Following conditioning trials, females were tested for a conditioned place preference. The findings indicate that female rats develop conditioned place preferences for paced sex and for sex in which the male is removed at her preferred interval. This suggests that sexual behavior is reinforcing to female rats when their preferred interval is achieved, whether or not they are actively controlling the rate of copulation.