Intralimbic evoked potentials in the formation of an instrumental food conditioned reflex to hippocampal electrostimulation in dogs]

In dogs with the electrodes implanted in the hippocampus, amygdala, septum and hypothalamus an instrumental alimentary conditioned reflex (CR) was elaborated to electrostimulation of the hippocampus. Intralimbic evoked potentials (EPs) were studied during the elaboration and extinction of this reflex and during stimulations of limbic structures conducted with the purpose of CR generalization checking. Late EP components in the lateral hypothalamus and central nucleus of the amygdala changed during CR elaboration and extinction and in the hippocampus during amygdala testing. In both cases the amplitude of trace positivity and of slow negative wave was less, when during stimulation of the structure an instrumental movement was initiated than at its absence.     

Functional organization of limbic brain structures during conditioned reflex activity in the dog

In experiments on 3 dogs it was shown that instrumental defensive conditioned reflex (CR) to electrical stimulation of the hippocampus is generalized within the limbic system (LS). The rate of generalization depended on the place of testing stimuli in LS. Stimulation of the medial parts of LS at the stage of stabilized initial reflex did not produce the generalized CRs, while they appeared distinctly in response to stimulation of the lateral parts of LS. In the process of elaboration of heterogeneous CRs (defensive and alimentary) to electrical stimulation of the hippocampus, generalized conditioned reactions from some brain structures appeared in both situations to the same degree while from other structures--with considerable differences. These data point to a possible participation in the genesis of the generalized CRs both of signal and reinforcing brain mechanisms.     

Switching off of granule cells after intrahippocampal injection of colchicine eliciting the disappearance of evoked potentials and a deterioration in the development of a conditioned avoidance reflex in rats

The aim of the work was to study the involvement in the process of learning of synapses between the perforant path and granular cells of the hippocampal dentate fascia for formation of conditioned reflex (CR) of active avoidance elaborated in response to electrostimulation of the perforant path. For solving this task, the property was used of the neurotoxin colchicine in a definite concentration to abolish selectively the fascia cells. One month after colchicine injection, destruction of granular cells was observed, disappearance of the dentate fascia focal evoked potentials and considerable deterioration of elaboration of active avoidance CRs. Administration of saline solution in control experiments did not elicit such changes. The obtained results show the decisive role of entorhinal input to the hippocampus in the used learning model.     

The role of the basal ganglia in the reproducibility of instrumental reactions acquired to electrostimulation of the hippocampus

In dogs with electrodes implanted into the brain, a defensive instrumental conditioned reflex (CR) was elaborated to light flashes, stimulation of the dorsal hippocampus (DH) and caudate nucleus (CN) stimulation. Reproducibility of the learned movement was tested for the contralateral DN, CN, nucleus accumbens (AN) and pallid globe (PG). In the second series the percent of the elicited movements was compared to EPs, appearing in response to signal and testing stimulation. The degree was elucidated of structures participation in motivational, signal and executive links of CR. Low degree of AN participation in the executive CR link (2-nd series) and a high degree of AN and PG participation in the signal link (3-d series) were shown. Thus, intrasystemic CR generalization was more effective than the intersystemic one.     

The role of signal and motivational links of a conditioned reflex in the initiation of instrumental movements in dogs

Alimentary instrumental conditioned reflex (CR) was elaborated in dogs to light flashes (I series), electrostimulation (ES) of the hippocampus (II series) and the hypothalamus (III series). Nonreinforced ES of the hypothalamus, amygdala, hippocampus and septum reproduced pressings on the pedal to the least extent in the I series (17-40% of trials), increasing in the II-nd one up to 40-87% during stimulation of the lateral hypothalamus, medial amygdala and contralateral hippocampus. In the III-rd series the number of pressings increased statistically significantly in comparison with the I-st series for most structures. Probably, besides the artificial increase of motivation during ES of the limbic structures which took place in all series, in the II-nd and III-rd series significance for movement reproduction was acquired by CR generalization appearing due to close interconnection of the structures. In this phenomenon connections (evaluated by the EPs) from the tested structures to the initially signal one are important.     

Conditioned reflex changes in the intra-analyzer interaction of the afferent inputs from the lateral geniculate body and pulvinar thalami in the cerebral cortex of cats

Paired heterogeneous stimulation of the lateral geniculate body (LGB) and pulvinar (Pulv) as a conditioned stimulus of alimentary instrumental conditioned reflex (CR), resulted in a change of relations between afferent inputs from LGB and Pulv to the visual and associative cortex of cats. At stimulation of LGB preceding by 40 ms, facilitation of the response to testing Pulv stimulation observed in untrained cats, appeared only at the beginning of the learning and was suppressed by the end of elaboration, when the amplitude of the response to the conditioning LGB stimulation greatly increased. In the process of CR elaboration (in the middle of learning), Pulv stimulation preceding by 40 ms facilitated the response to the testing LGB stimulation and simultaneously increased the amplitude of the response to the conditioning Pulv stimulation.     

Reproduction of electrographic correlates of a conditioned reflex after changes in the activity of the noradrenergic and dopaminergic systems

On the model of shortly delayed defensive conditioned reflex in cats, it was shown in acute experiments that pharmacologically elicited change of NA system activity (clonidine, 0.2 and 1.5 mg/kg intravenously) and of DA system activity (apomorphine, 3 mg/kg intravenously) leads to a definite manifestation of electrographic correlates of memory trace, i.e. of conditioned evoked potential (EP) in examined brain structures, as well as of conditioned neurographic response (CNR) and conditioned skin-galvanic reaction (SGR). The increase of the NA system activity causes a rise of the number of conditioned EPs in the reticular formation, hippocampus and preoptic area along with an enhancement of CNR reproduction. The increase of the DA system activity contributes to the appearance of conditioned EPs in the hippocampus, amygdalar complex and central gray matter, together with an enhancement of the reproduction of conditioned SGR.     

Effect of hippocampal stimulation on the feeding behavior of cats

Influence of electrical stimulation (100 cps., 1.0 ms) of medial parts of dorsal and ventral hippocampus (field CA1), and the lateral parts of dorsal and posterior hippocampus (field CA3) on general behaviour, elaboration of instrumental and manifestation of delayed reactions was studied in chronic experiments on cats. Stimulation of medial parts of dorsal and ventral hippocampus elicited a reaction of orienting reflex type to natural stimuli. Stimulation of lateral parts of dorsal and posterior hippocampus evoked arrest reactions. Medial and lateral parts of hippocampus produced different influences on elaboration of conditioned reflexes. In the first case elaboration was possible, but developed slower, while in the second case the ability to learn during stimulation was completely lost due to development of arrest reaction. Stimulation of different parts of the hippocampus disturbed delayed reactions, reducing the number of correct responses.     

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.     

Emotional stress during conditioned reflex transformation of heterogeneous instrumental reflexes

The factors leading to pronounced emotional stress accompanied by changes in electrical activity of hippocampus were studied in four dogs during elaboration of conditioned switching-over of heterogeneous instrumental reflexes. Objectively recorded signs of emotional stress were observed in two cases: when the animal was not accurate enough in discerning defensive and alimentary situations and throughout the improvement of instrumental defensive reflex. Pronouncement of hippocampal theta-rhythm increased at those stages of switching-over elaboration where the probability of successful avoiding pain stimulation was relatively low. The data obtained permit the conclussion that theta-rhythm is the correlate of the degree of the emotional stress and not only a manifestation of general arousal reaction depending on the level of sensory input.     

A collector of evoked potentials]

The collector is an adaptive algorithm for pattern recognition. It proposes new in-line fully-automatic technique to learn and recognize effective patterns of input data stream. Evoked potentials (EP) were recorded by ADDA 100 KHz, 4 channels, and described by 200 points per each EP. The collector recognized different studies of conditioned response (CR) by patterns of EPs in amygdalar central nucleus. In dogs with implanted into the limbic structures concentric electrodes an instrumental CR was elaborated to electrical stimulation of the dorsal hippocampus. Generalization or transfer of this CR was tested by means of electrostimulation of amygdalar basal nucleus. The generalization in the first experiment took place approximately in 86% of cases, in the second one in 52% of cases. In the first experiment the amplitudes of initial negativity and of late positive waves were smaller than those in the second one and in the experiments before conditioning.     

Mechanism of the generalization of a conditioned reflex elaborated to electrostimulation of the brain in dogs

To study functional connections in the limbic system (LS), a model was used of instrumental alimentary CR, elaborated in response to low-frequency hippocampus electrostimulation with testing of its generalization within the LS. The dependence was established of the generalization on activation of corresponding pathways between the signal and tested brain structures, the activation of pathways was estimated by EPs recorded in limbic structures in response to hippocampus stimulation (during CR performance), or vice versa (in generalization trials). It turned out that for the appearance of CR generalization, two-way connections between signal and tested brain structures or connections only to the signal structure are more important. One-way connections from the signal structure to tested ones, judging by data, are not important for appearance of the CR generalization in used model of conditioning.     

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.     

The possibility of elaborating conditioned reflexes on the basis of emotional reactions evoked by electrical stimulation of limbic structures]

In experiments on cats with chronically implanted electrodes a conditioned stimulus (200 c/s tone) was paired with electrical stimulation of limbic structures, which produces pronounced emotional behaviour: defensive, aggressive, alimentary or drinking reactions. It has been shown that conditioned reactions are not elaborated on the basis of electrical stimulation, which activates alimentary, drinking or aggressive behaviour. Neither is a conditioned reflex formed to the combination of sound and stimulation of the brain structures, which inhibits alimentary behaviour. A distinct conditioned fear reaction sets in as a result of combination of sound and electrical stimulation of brain structures, which evoke defensive behaviour. The data obtained are analyzed in the light of the significance of natural requirements of the organism for the elaboration of conditioned reflexes.     

Conditioned modification of viscerosensory evoked potentials during sleep and wakefulness in cats

The effects of classic conditioning on the viscerosensory evoked potentials (EPs) were studied in twenty cats during wakefulness (W), slow-wave-sleep (SWS) and paradoxical sleep (PS). Four types of the experiment were performed on four groups of animals. Weak, non-painful stimulation of the small intestine or of the left splanchnic nerve was used as conditional stimulus (CS) in all experiments. A painful or non-painful shock on the left radial nerve served as unconditional stimulus (US) which followed the CS with a delay of 500 ms. In the first and second series of experiments, the CS was paired with non-painful or painful CS during W. In the third and fourth types of experiment, weak US was used and conditioning was done during SWS or PS. The evoked responses were recorded from the primary (SI) and secondary (SII) somatosensory and associative (AS) cortex, the thalamus (VPL), hypothalamus (HPT) and dorsal hippocampus (HPC). In each experiment, the stimulus pairings resulted in a complex electrographic conditional response (CR) which included an amplitude increase of the late components of EP's (early CR) and the development of a wave of 500 ms latency (delayed CR). In the second experiment, however, a behavioural CR (limb flexion) also appeared. All these CRs proved to be extinguishable. The recall of CR established during W was successful in SWS. The traces of CS-US pairings during SWS could, however, be elicited only in SWS. Both establishment and recall of CR were unsuccessful during PS. The possible mechanism of the effects originating from an interaction of conditioning and sleep on the viscerosensory inputs of the brain are discussed.     

The neuronal organization of a focus of conditioned excitation in the cat sensory-motor cortex]

The activity of single units in the focus of conditioned excitation was studied during defensive conditioning to direct electrical stimulation of the cat sensorimotor cortex. Reorganizations of spike activity set in during the period of reflex elaboration, were manifest in the increased number of excited neurones and those which respond both to the conditioned and unconditioned stimuli. In the course of elaboration, the inhibitory phase of unit responses to direct electrical stimulation of the sensorimotor cortex was reduced, while the frequency of background unit spike activity was enhanced. Acute extinction of the reflex restored the initial duration of the inhibitory phase and reduced the frequency of the background activity.     

Features of the formation of conditioned secretory reflexes in response to the stimulation of different areas of the caudate nucleus of the dog

Properties were studied of elaboration of conditioned alimentary secretory reflexes to threshold electric stimulation of the caudate nucleus in dogs. The rate of formation of such a reflex and its magnitude were considerably lower than in reflexes elaborated to distant stimuli. Latencies were longer; dynamics of conditioned and unconditioned secretory reactions was similar to that of reflexes to a weak stimulus--light. The motor component of the conditioned alimentary reaction, as a rule, was absent. Characteristics were revealed of formation of alimentary reflexes to stimulation of the dorsal and ventral parts of the head and body of the caudate nucleus.     

Tonic and phasic modifications of viscerosensory evoked potentials during sleep in cats

Modification of the viscerosensory evoked potentials (EPs) were studied during the sleep-wakefulness cycle of the rat. Electrical stimuli of various intensity were delivered either to the mucosal surface of a fistula of the small intestine or to the left splanchnic nerve during wakefulness (W), drowsiness (D), slow-wave-sleep (SWS), and paradoxical sleep (PS). The average EPs were recorded from the somatosensory (SI and SII) and associative (AS) areas of the cortex, the ventrobasal complex of the thalamus (VPL), the posterior hypothalamus (HPT) and the dorsal hippocampus (HPC). The amplitude of each component of the EPs in all explored structures were the largest in SWS and the smallest in W. A phasic increase in amplitude was observed in the EPs recorded immediately before the appearance of the spindles of SWS and during the REM episodes of PS. The peak latencies of the late components were the longest in SWS. These changes of the amplitudes and latencies were greater in the responses to weak stimulation than in EPs to strong ones. The possible synaptic events of the sleep-dependent control of viscerosensory activity are discussed.     

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.     

The long-term effect of acute hypoxic hypoxia on shuttlebox avoidance learning in rats

Long-term influence was studied of the acute hypoxic hypoxia seance on rats behaviour in situation of elaboration of the conditioned reaction of active avoidance of electric shocks in shuttle chamber. It was found that in 2.5-3 months after the hypoxia seance, the experimental animals significantly differed from the intact controls by dynamics of CR elaboration (rats which had hypoxia were ahead of the control ones) and by distribution of the conditioned reactions latencies (for experimental animals this distribution was shifted to minor values). The character of these behavioural shifts coincided with that observed in the group of rats with local unilateral hippocampus lesion. The obtained results and numerous data presented in literature on the influence of the hippocampus lesion on animals shuttle avoidance learning, allow to conclude that the seance of hypoxic hypoxia leads to the disturbance of the hippocampus function. This conclusion conforms to the data on diffusive death of the hippocampal and neocortical neurones as a result of hypoxia action.