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.     

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.     

Effect of regular electrical stimulation of the septum on defensive conditioning

A conditioned defensive reflex to photic stimulation was produced in rabbits in computer-controlled experiments during regular electrical stimulation of the septum. During reflex formation spectral-correlation analysis was undertaken of sensomotor and visual cortical potentials and hippocampal potentials. In each rabbit the reflex to light was produced during septal stimulation at a definite frequency (2, 4, 7, and 9 Hz). Regular electrical stimulation of the septum at frequencies of 7 and 9 Hz accelerated conditioning whereas stimulation at a frequency of 2 Hz prevented formation of the temporary connection (the reflex appeared at the 35th combination). By changing the frequency of electrical stimulation of the septum, the speed of learning can thus be influenced. It is suggested that the role of the septum is to set a definite level of synchronization of brain processes at the optimal value for conduction of excitation from its afferent to its effector system.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 10, No. 3, pp. 239–244, May–June, 1978.     

The disinhibitory influence of the activating system when artificially excited from different points in the brain]

EEG activation can be produced by electrical stimulation of some cortical points with the same threshold current strength as by the midbrain RF and thalamic CM stimulation. Near-threshold stimulation of all these points acting simultaneously with inhibitory conditioned signals does not disturb the effector inhibition but displays an EEG difference between negative signals: the fine differentiation sound evokes considerable EEG desynchronization, while the rough one does not change the background rhythms. The same stimulation combined with a positive signal which has been made ineffective by successive inhibition or extinction, reestablishes the intensive EEG activation in response to this signal and the effector conditioned reflex. Therefore a mode-rate additional stimulation of the activating points in the cortex, RF and CM has a disinhibitory influence. When initiated in the cortex this influence may be transmitted from the cortical point to other parts of the brain along transcortical and corticofugal connections.     

Neuron activities of the motor cortex during conditioned eye blink reflex in rabbits (author's transl)]

Effects of the tone (CS) on neurons of the motor cortex were investigated in naive, pseudoconditioned, and conditioned rabbits. Conditioning to eye blink reflex was made by a combination of CS and air puff (US). Effects of electrical stimulation of the subcortical structures were also observed on the cortical neurons associated with the conditioned reflex. The results were as follows. (1) Proportion of neurons which significantly increased the firing rate in response to the CS, type E, was higher in the conditioned group than in other two groups. On the other hand, no group difference was found in the proportion of neurons which significantly decreased the firing rate to the stimulus, type I. (2) Most of the type E neurons in the conditioned rabbits began to fire at latencies of about 50 to 100 msec after the CS, preceding about 200 msec to the appearance of the peripheral conditioned responses (EMG). (3) Most of the type E neurons in the conditioned animals were more easily affected by stimulation of the medial geniculate body and the brain stem reticular formation. Based on the results mentioned above, it is concluded that in the rabbits conditioned to the eye blink reflex, excitability of neurons in the motor cortex is enhanced by the tone (CS), and by electrical stimulation to the medial geniculate body and the brain stem reticular formation.     

Systems organization of cerebral processes in the cat during learning while undergoing electrical stimulation of the neocortex

A delayed spatial choice (DSC) was elaborated in five cats during electrical stimulation (ES) of the frontal cortical parts with a frequency of 80 imp/s. Then the task fulfillment was tested following cessation of the electrostimulation or under the action of other current frequencies (35,3 and 120 imp/s). The number of erroneous choices increased in the absence of ES or during 3 imp/s ES of the frontal parts. The effects of frequencies of 35,80 and 120 imp/s did not differ. Three cats were trained to DSC without ES. The conditioned reflexes were tested during ES of the frontal cortical parts with current frequency of 3 and 80 imp/s. Statistically significant increase of the number of erroneous responses took place in both situations. The obtained data are discussed from the point of view of the integrative activity of the cerebral structures in DSC. Its disturbance during ES of the cortical zones and dissociation (discordance) after cancellation of stimulation during which the conditioned reflex had been elaborated, point to systemic organization of brain functioning in goal-directed forms of behaviour.     

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.     

Investigation of pallidofugal influences on hypothalamic activity

In chronic experiments on nine cats electrical stimulation of the posterior zones of the lateral hypothalamus led to reproduction of a conditioned food-getting reflex produced previously in response to clicks. During stimulation of the globus pallidus a food-getting reflex also appeared in 3 of 10 zones studied, but it did so only irregularly. In response to combined stimulation of the hypothalamus and these three zones of the globus pallidus facilitation of this reflex was observed: its intensity was increased and its latent period shortened. Stimulation of other areas of the globus pallidus inhibited the food getting reflex of hypothalamic origin on account of the intensification of purposeless motor responses. Stimulation of the globus pallidus evoked desynchronization of spontaneous hypothalamic electrical activity. After bilateral electrolytic destruction of the globus pallidus and its principal efferent pathway (the ansa lenticularis) no conditioned food-getting reflex was reproduced during hypothalamic stimulation. After pallidectomy the amplitude of the spontaneous waves and evoked potentials was reduced by a statistically significant degree in the hypothalamic zones tested. The results are evidence of the existence of regulatory functional influences of the globus pallidus on the lateral hypothalamus.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 6, No. 6, pp. 592–601, November–December, 1974.     

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.     

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.     

Level of neuroactive steroids in the brain, and gender-related differences in formation and decrease of conditioned reflex in rats

We investigated gender-related differences in dynamics of the brain sexual steroids during learning and the decrease of conditioned reflex in the modeling experiment. It was revealed that, before training to conditioned reflexes, females manifested a greater anxiety than males. Significant differences between males and females in formation of the conditioned reflex of passive avoidance were not revealed, whereas the conditioned response decrease were by 2-3 days faster in male rats than in females. It was revealed that there was an increase of testosterone content in various structures of the brain, especially in hippocampus and frontal cortex with its constant level in the blood plasma in learning conditioned response of passive avoidance in male adult rats. Also an increased estradiol concentration was found in females' amygdale, while increased value of estradiol was detected in hippocampus and the singular cortex in decrease of the conditioned response of passive avoidance. In blood plasma, the testosterone level was not changed, and the estradiol concentration was reduced significantly after the decreased conditioned reflex. Different dynamics of changes in the levels of sex steroids in the brain and the blood plasma can indicate a probability of their formation in nervous tissue. The correlation analysis confirms the conception about selective involvement of the brain's testosterone and estradiol in the specific structures in realization ofthe learning and memory processes in adult male and female rats.     

Evoked potentials during the elaboration of a conditioned reflex to hippocampal stimulation in rats

In experiments on 9 rats, the study of evoked potentials (EPs) of the CA1 field of the dorsal hippocampus to stimulation of its symmetrical part serving as a signal of drinking conditioned reflex (CR) showed that during reflex elaboration, the amplitude of the main EP components significantly decreased; CR did not appear when the population spike (PS) was absent in the hippocampal response. PS always accompanying CR was not specific only of it, it was also recorded at other behavioural reactions. Changes of fascia dentata EPs in the process of CR elaboration to stimulation of its symmetrical part consisted in decrease of the initial negative wave and increase of the positive one. The obtained data point to a significant reconstruction of excitatory and inhibitory inputs to the hippocampus and fascia dentata under the influence of conditioned activity.     

Functional differentiation of the theta-rhythm of the hippocampus in the cat

On the model of discriminating alimentary conditioned reflex with spatial separation of the sources of conditioned (CR, light flashes) and unconditioned (feeding trough) stimuli the theta-rhythm of the dorsal hippocampus was evaluated in cats. Two types of the theta-rhythm were observed in the spectrum of the hippocampal electrical activity: low-amplitude, consisting of a slow growing theta-waves (type I) and high-amplitude consisting of rapidly increasing theta-waves (type II). The type I theta-rhythm is sensitive to noradrenaline and correlates with behavioural forms directed immediately to the realization of alimentary motivation, while the type II is sensitive to serotonin and correlates with behavioural forms directed to the source of the conditioned stimulus. Enhancement of the type II theta-rhythm takes place during a delay of the expected conditioned stimulus. It is suggested that type I theta-rhythm reflects a level of activity of the brain structures connected with unconditioned mechanisms, with realization of biological motivations, while type II theta-rhythm is connected with conditioned reinforcing stimuli; it correlates with various forms of conditioned orienting reflexes and reflects the work of the "nervous model of reinforcing stimulus".     

Generalization of an instrumental defensive conditioned reflex elaborated to electric stimulation of the hypothalamus in dogs

Generalization of defensive conditioned reflexes elaborated to electrical stimulation of the lateral hypothalamus (LH) was studied in four dogs with electrodes implanted in various structures of the limbic system. Electrocutaneous stimulation was switched off when the dog lifted the foreleg to a definite level. Generalization of the conditioned reflex was manifested in different degrees when testing different formations of the limbic system, or testing one and the same structure, but at different stages of conditioning. Two types of generalization were found: the first one--a well pronounced motor reaction, by its latency, level and duration of lifting the foreleg similar to movements appearing in response to the conditioned stimulus; and the second one--low amplitude or short-term movements differing from conditioned ones. The first type of generalization was observed in response to stimulation of LH, contralateral to the point of signal stimulation, of the ventromedial hypothalamic nucleus, the mammillary bodies and the basal, lateral and to a lesser degree, the central nucleus of the amygdaloid complex; the second type--in response to stimulation of the ventral hippocampus, the medial and lateral septum nuclei.     

Level of neuroactive steroids in the brain and sex-related peculiarities of formation and extinction of conditioned reflex in rats

Sex-related peculiarities of dynamics of brain sex steroids in the process of learning and extinction of the conditioned reflex of passive avoidance have been studied in model experiment. Prior to learning of the conditioned reflex, female rats were found to be distinguished by manifestation of anxiety and fear as compared with male rats. At formation of the conditioned reflex, no significant sex-related differences were detected between males and females, whereas extinction of the conditioned reaction of passive avoidance in males occurred by 2–3 days faster than in females. At learning of conditioned reaction of passive avoidance, in sexually mature male rats there was revealed an increase of the testosterone content in various brain structures, especially in hippocampus and frontal cortex, while its level in blood plasma remained unchanged. Also shown was an elevation of estradiol concentration in female amygdale, whereas at extinction of the conditioned reaction of passive avoidance, a rise of estradiol values was noted in hippocampus and cingular cortex. At the same time, the testosterone level in blood plasma did not change, whereas after extinction of the conditioned reflex the estradiol concentration decreased statistically significantly. Different dynamics of changes of the sex steroid levels in brain and blood plasma can indicate a possibility of their formation in the nervous tissue. The performed correlation analysis confirms the concept of selective involvement of testosterone and estradiol of individual brain structures in realization of processes of learning and memory in sexually mature male and female rats.     

Effect of electric stimulation of non-specific and specific thalamic nuclei on the spatial synchronization of cortical potentials in the rabbit

The effect of low-frequency (1-10 Hz) electrical stimulation of nonspecific n. centralis lateralis and n. centrum medianum and specific thalamic (LGB) nuclei on spatial synchronization of biopotentials of neocortical areas and on the process of learning was studied on rabbits. Electrical stimulation of the non-specific nuclei raised the level of correlation of the cortical potentials, while the LGB stimulation, on the contrary, weakened the spatial synchronization between the potentials of the visual and sensorimotor neocortical areas. On the basis of the obtained data a conclusion is made that stimulation of the non-specific thalamus contributes to a more successful formation of defensive conditioned reflex to light unlike LGB stimulation. It is suggested that a certain specificity of the studied subcortical formations in organization of spatial synchronization of the brain biopotentials and in the process of learning is due to morpho-functional peculiarities of these structures.     

Self-deprivation of paradoxical sleep in cats

The phenomenon of paradoxical sleep (PS) self-deprivation has been detected and described. The self-deprivation is acquired just as a classical conditioned reflex during enforced PS deprivation both by water tank procedure and by the animal's awakenings in response to sensory stimuli or direct electric stimulation of activating structures of the midbrain and diencephalon, following the transition of slow-wave sleep to PS. In this situation the transition of the brain from one physiological state to another is a conditioned signal, and sensory stimulation or brain stimulation, resulting in arousal reaction, serves as an unconditioned stimulus. It is suggested that the detection and analysis of PS self-deprivation are of a great importance, on the one hand, for correct understanding of the functional significance of this physiological brain state, and, on the other hand, for accurate analysis and assessment of the dissociative processes, observed during PS deprivation and postdeprivation period.     

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 effect of ablation of the caudate nucleus on the alimentary zone of the lateral hypothalamus]

A conditioned food-procuring reaction previously elaborated to an acoustic stimulus was reproduced in chronic experiments on six cats by means of direct electrical stimulation of the posterior parts of the lateral hypothalamus. Folloiwng extensive bilateral electrolytic ablation of the caudate nucleus, conditioned food-procuring reaction to the stimulation of the hypothalamus could not be reproduced for 40 to 70 days. The conditioned foor-procuring reflex to the acoustic stimulus disappeared for 14 to 30 days to be subsequently spontaneously restored. After caudatotomy, a diminution of the average amplitude of background oscillations and of evoked potentials to acoustic stimuli was recorced in the examined zones of the lateral hypothalamus. The part played by the caudate nucleus in the processes of alimentary behaviour activation is discussed.