Dynamics of the spectral composition of the hippocampal theta-rhythm in the dog during switching-over of heterogeneous instrumental reflexes

In two dogs with electrodes chronically implanted in the hippocampus, hippocampal electrical activity and the heart rate were recorded in the process of elaboration of a conditioned switch-over of operant alimentary and defensive responses. Averaged computerized spectral characteristics of hippocampal theta-rhythm were essentially different between the alimentary and defensive situations in intersignal period as well as during the action of triggering conditioned stimulus. Individual differences in the dominant frequency of bioelectrical activity were observed. The animal with a higher theta-rhythm frequency elaborated conditioned switch-over of heterogeneous operant responses sooner and more successfully.     

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".     

Conditioned reflex and electrical activities of the hippocampus during the random use of heterogeneous triggering stimuli

In dogs with electrodes chronically implanted in the hippocampus, the conditioned activity, heart rate frequency and spectral characteristics of the hippocampal theta-rhythm were studied in conditions of irregular presentation after a preparatory stimulus now of alimentary and now of defensive triggering conditioned stimuli. It is shown that uncertainty of alimentary or defensive reinforcement is a stronger emotiogenic factor than the action of the triggering defensive conditioned stimulus. Changes in electrical hippocampal activity and autonomous activity depend, along with other factors, on forecasted volume of the forthcoming motor activity. The speed of instrumental conditioned reflexes formation correlates with the hippocampal theta-rhythm frequency, typical for the given animal.     

Changes in the frequency of the hippocampal theta-rhythm in the dog exposed to a conditioned food stimulus

Frequency changes of hippocampal theta-rhythm in the process of elaboration of coinciding or delayed instrumental alimentary reflex was studied in two dogs. Determination of dominating frequency of rhythmical activity was carried out by means of mathematical methods of analysis on a computer. It was found out, that during the action of conditioned alimentary stimulus the frequency of dominating oscillations became enhanced. Animals with a more frequent initial theta-rhythm formed the delayed alimentary reflex more rapidly.     

Instrumental heterogeneous responses to 2 successive complex stimuli with a common initial stimulus in the dog

Formation and achievement of heterogenous instrumental reflexes to two consecutive complex stimuli was studied in dogs. Under the action of conditioned complex stimulus tone--Pause--tone, the dogs may be trained not to have a motor response to the first tone presentation, but perform alimentary instrumental reaction only to its repeated administration. Introducing into the experiment not only alimentary but also defensive complex stimulus stone-pause--light resulted in a change in animal's reactions in such a sequence: at first alimentary instrumental reaction was disinhibited under the action of the preparatory stimulus and during the pause, then bieffector responses appeared, further on in most of the dogs motor defensive reactions mainly took place. Trigger stimuli evoked the adequate instrumental reaction.     

The interaction of the serotonin and dopaminergic systems of the brain in the mechanisms of latent inhibition in rats

Decrease of serotonin concentration in the septo-hippocampal region of Wistar male rats was obtained by introduction of 5,7-dihydroxytryptamine in the raphe median nucleus. In seven days, after 20 pre-expositions of the conditioned stimulus (presentation of the experimental chamber) conditioned reaction of passive avoidance was elaborated. In sham-operated control the pre-exposition of the conditioned stimulus caused latent inhibition, determined by several parameters: low level of conditioned reaction reproduction, its prolonged preservation at the formed level and nonsubjection to amnesia. Introduction of haloperidol in a dose of 0.5 mg/kg one hour before learning restored the state of latent inhibition disturbed by switching off of the mesolimbic serotonin system. It is supposed that in the state of pre-exposition, the decrease of attention to nonreinforced stimulus takes place because of the intensification of inhibitory influence of the serotoninergic system and reciprocal decrease of dopaminergic system activity.     

Effect of anticholinergic drugs alone and in combination with nembutal on burst theta-neurons of the rabbit septum

Activity of neurones with rhythmic theta-bursts was recorded in the medial septum--diagonal band complex of the waking rabbits with intact and deafferented septum. Effects of anticholinergic (scopolamine, atropine) and cholinomimetic (physostigmine) drugs were investigated after i.v. injection. Cholinoblocking drugs in doses, suppressing the theta-rhythm in the hippocampal EEG, eliminated rhythmic activity in some cells with weak theta-modulation. Theta-bursts persisted in cells with stable continuous rhythmicity, though its regularity decreased in some of them. Strong reticular or sensory stimulation evoked an increase of burst frequency, involvement of additional septal cells into rhythmic activity and appearance of the theta-rhythm in the hippocampal EEG. Neither anticholinergic, nor cholinomimetic drugs influenced the frequency and basic characteristics of theta-bursts in any condition tested. The anticholinergic drugs have no selective effect upon low-frequency theta-bursts. The septohippocampal connections contain a significant non-cholinergic component. The theoretical concept of the septum as a sole source of the whole frequency band of the theta-rhythm is proposed.     

Spectral correlation parameters of neocortical potentials in the rabbit undergoing paired isorhythmic stimulation

At pairing of isorhythmic stimuli beyond the theta-rhythm frequency limits (3 and 8 Hz), in power spectra of EEGs of the sensorimotor and visual neocortical areas of rabbits, the frequencies are present both of the theta-range and of the stimulation frequency, in the background activity as well as during the stimulation. Both rhythms are in reciprocal relations. The frequency of the theta-rhythm approaches the frequency divisible by that of the stimulation. Under the action of the conditioned stimulus, crosscorrelation coefficients (CC) between the potentials of the areas under study decrease in most cases in comparison to their background values. Combination of the conditioned stimulus with the unconditioned one, leads approximately in equal number of cases to an increase or decrease of CC. After elimination of the stimuli, in most cases CC increases. CC of the background activity does not increase in the course of paired stimuli presentation though a conditioned response is being formed. At presence of stimuli frequency fluctuations simultaneously in the potentials of both areas, the rise of coherence function at this frequency does not occurs always. Thus, the above spectral-correlation parameters of rabbit's cortical potentials differ from those which arise at pairing of continuous nonrhythmic stimuli. This difference is probably due to different characteristics of the stimuli presented.     

Developmental caspase-3 activation in the rat hippocampus is involved in the maturation of instrumental behavior

Previously the developmental switch to caspase-3 activation in the rat hippocampus has been shown during the third week of life. The goal of this study was to explore effects of caspase-3 inhibition during this period on learning in a two-way avoidance paradigm. On postnatal day 18, the pups were intracerebroventricularly administered with caspase-3 inhibitor Z-DEVD-FMK. Control groups were injected with either the control peptide Z-FA-FMK or saline. Caspase-3 inhibition, naturally activated in this critical period, was found to disturb the maturation of instrumental behavior. In particular, the young adult rats of Z-DEVD-FMK group displayed less effective elaboration of escape and active avoidance reactions in two-way avoidance paradigm, accompanied with a decrease in inter-trial crossings. However, associative components of the learning did not change after caspase-3 inhibition. Conditioned emotional behavior was, in general, similar in all groups, and the number of responses related to conditioned stimulus exploration did not differ in Z-DEVD-FMK and Z-FA-FMK groups. In spite of the deficit in active avoidance conditioning in Z-DEVD-FMK group, a significant increase in incomplete or preparatory reactions to conditioned stimulus was demonstrated suggesting that the association between predictive conditioned stimulus and possibility of crossing can be elaborated. The change of exploratory behavior is unlikely to be specific for caspase-3 inhibition, being similar in Z-DEVD-FMK and Z-FA-FMK groups.     

Role of the hippocampal theta rhythm in developing the anxiolytic action of phenazepam

It has been found in experiments on rats with chronically implanted electrodes that water-deprived rats as well as those under the conflict-punishment conditions demonstrated considerable activation of the hippocampal theta-rhythm. Phenazepam decreased the hippocampal theta-rhythm in water-deprived rats, whereas electric punishment did not produce any appreciable changes in the frequency spectrum on the electrogram. The data obtained suggest that an anticonflict (anxiolytic) effect of benzodiazepines is caused by the regulatory influence on the theta-rhythm in the hippocamp.     

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.     

Hippocampal State-Dependent Behavioral Reflex to an Identical Sensory Input in Rats

We examined the local field potential of the hippocampus to monitor brain states during a conditional discrimination task, in order to elucidate the relationship between ongoing brain states and a conditioned motor reflex. Five 10-week-old Wistar/ST male rats underwent a serial feature positive conditional discrimination task in eyeblink conditioning using a preceding light stimulus as a conditional cue for reinforced trials. In this task, a 2-s light stimulus signaled that the following 350-ms tone (conditioned stimulus) was reinforced with a co-terminating 100-ms periorbital electrical shock. The interval between the end of conditional cue and the onset of the conditioned stimulus was 4±1 s. The conditioned stimulus was not reinforced when the light was not presented. Animals successfully utilized the light stimulus as a conditional cue to drive differential responses to the identical conditioned stimulus. We found that presentation of the conditional cue elicited hippocampal theta oscillations, which persisted during the interval of conditional cue and the conditioned stimulus. Moreover, expression of the conditioned response to the tone (conditioned stimulus) was correlated with the appearance of theta oscillations immediately before the conditioned stimulus. These data support hippocampal involvement in the network underlying a conditional discrimination task in eyeblink conditioning. They also suggest that the preceding hippocampal activity can determine information processing of the tone stimulus in the cerebellum and its associated circuits.     

The dependence of the dynamics of the extinction of a temporary connection on the recognizability of a reinforcing stimulus]

Dynamics was studied of the extinction of temporary connection, elaborated by means of motivationally significant word, in patients with chronic alcoholism. Two series of studies were conducted. In the first one the reinforcing stimulus was not recognized by the subject and was perceived as a dull light flash on the screen. In the second one the word was easily read, i.e. it was recognized. It was found that conditioned changes of P300 wave at the elaboration of temporary connection depend on the recognition of the reinforcing stimulus. Temporary connections, elaborated by non-recognized motivationally significant stimulus are considerably stronger that the connections, elaborated by means of recognized reinforcement.     

Habituation in the rabbit visual cortex during development and after septal ablation

In chronic experiments on adult rabbits with injury to the septum pellucidum and on newborn rabbits the dynamics of evoked responses to repeated flashes was studied. Experimental blocking of the hippocampal theta-rhythm by electrolytic destruction of the medial septum is followed by marked facilitation of habituation of the primary responses. This process takes place twice as fast in rabbits with damage to the septum as in intact animals. Very rapid habituation of the primary responses was observed in newborn rabbits before acquiring vision and in rabbits with vision but under the age of 15–16 days, after 10–20 presentations of the stimulus. When the animals reached this age the time required for habituation increased sharply. Starting from the age of 17 days, the primary responses of the animals were just as stable as in normal adult rabbits. The significance of the hippocampal theta-rhythm as a factor preventing the development of habituation is discussed.Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 4, No. 2, pp. 123–129, March–April, 1972.     

Effect of electrocoagulation of the septum on the behavior and memory of the cat

Lesion effects of various areas of the septum on general behaviour, learning and memory were studied in cats. It appeared that electrocoagulation of the medial septum alone leading to the disappearance of the hippocampal theta rhythm does not result in the development of the septal syndrome signs; does not disturb the normal structure of the sleep-wakefulness cycle; does not delay the elaboration of instrumental alimentary reflexes (to approach two feeders) or their extinction, but does entirely disturb the delayed responses to conditioned stimuli. In cases when lesion involves also the lateral septum, it produces the development of all signs of the septal syndrome (hyperemotionality, hyperactivity, rage, hyperphagia, etc.), disturbance of the normal structure of the sleep-wakefulness cycle, delay of both the elaboration and extinction of instrumental alimentary reflexes, disturbance of pre-elaborated conditioned reactions with sound discrimination, entire disturbance of conditioned delayed responses. On the basis of these data, the specific significance of hippocampal theta-rhythm in the organization of learning and memory is rejected, and a more important role is attributed to the descending regulatory influence exerted by the hippocampus and other archipaleocortical structures on the activating and motivatiogenic structures of mesodiencephalon.     

Correlation of hippocampal theta-rhythm with behavior in rabbits]

Dynamics of the hippocampal theta-activity was studied during performance of a stably elaborated habit with drinking reinforcement. It has been shown that during running and in other forms of behaviour, belonging to the class of voluntary movements, the theta-activity takes place within the band of 7.5--12 c/s; during emotional stress without locomotion its frequency amounts to 6--7.5 c/s, during lapping movements it is equal to 5-6 c/s, during emotionally motivated and behavioral inactivation--to 2.5--5 c/s. In accordance with the data obtained in conditions of spontaneous behaviour, the observed facts allow to consider the wide spectrum of the hippocampal theta-rhythm not as a continuous, one-band, functionally uniform frequency, reflecting the continuum of arousal by its intensity,--but as consisting of discrete frequency bands which are functionally connected with different forms of behavior.     

Dynamics of the summary electrical activity of the dorsal hippocampus during development of experimental informational behavioral pathology

Dynamics of dorsal hippocampal EEG changes were traced in cats during the short-term memory loads under conditions of the time deficit between the separate delayed reactions. Shortening the intervals between the tests from 3-5 min to 15-20 s led to an expressed ECoG desynchronization accompanied by an initial increase and later blockade of the hippocampal theta-rhythm. Hippocampal theta-activity changes under conditions of the time deficit was a result of emotional stress. The long emotional stress impaired the short-term image memory, and this was manifested in hippocampal theta-rhythm disappearance.     

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.     

Neuronal activity of the cerebral cortex in cats with conditioned inhibition

Unit activity of the somatosensory cortex was studied in chronic experiments on cats during alimentary instrumental conditioned reflex performance and elaboration of conditioned inhibition (CI). First presentations of the CI signal at the beginning of CI formation caused, due to orienting reaction to a new stimulus, a levelling of the response of the neurones to the positive conditioned signal included into the CI complex. At the stage of consolidated CI, this depression proceeded gradually during the development of conditioned inhibition caused by consecutive presentations of the nonreinforced CI combination. Two groups of neurones were involved in the process of the CI performance: one of them being the same which was activated also in response to positive stimulation during performance of the conditioned response, and the second one being areactive to the positive conditioned stimulus but reducing the frequency of the background activity.     

Effect of extirpation of the sensorimotor cortex on the formation of conditioned reflexes to a complex signal in the ontogeny of the cat

In kittens of the age from 39 days to 4 months the influence was studied of the sensorimotor cortex (SMC) ablation on formation and preservation of previously elaborated reflex to a simultaneous complex stimulus (light + sound) with extinction of reaction to nonreinforced components of the complex signal. It is shown that SMC ablation in the age up to 2.5 months does not affect the formation or preservation of the conditioned reflex. The SMC ablation in preliminarily trained kittens in the age of 3.5 months and older leads to disinhibition of components differentiation with preservation of the positive conditioned reflex to the complex signal. In untrained kittens of the same age the SMC ablation leads to disability of animals to inhibit the motor reaction to differentiation signal. The question is discussed of SMC significance in the ontogenesis at formation of adequate forms of behaviour requiring heterosensory interaction.