DEBATE ON REPORT "THE ROLE OF THE SEPTO-HIPPOCAMPAL SYSTEM AND PARADOXICAL PHASE OF SLEEP IN THE REGULATION OF LEARNING AND MEMORY" OF PROF. T. ONIANI (THE 8th SYMPOSIUM "GAGRA TALKS" IN 1983)



B.I. Kotlyar. It is very seldom that an investigator can succeed in designing and carrying out experiments so that to receive unequivocal answers to the questions that are steadily being ascertained and on which there have been diverse persistent points of view. I congratulate you, prof. Oniani, on this success.

I have three questions to you:

1. Taking into account your findings, can you entirely share the known point of view that the hippocampus does not provide only any one function, e.g.; memory, information processing, the comparatory function, etc., but, together with other structures, is involved in creating a specific level of brain activation for each mode of behavior involving also the individually acquired one, and that the theta rhythm has no independent functional role and does not serve as a biological correlate for one state or one mode of behavior (voluntary movements, stress, etc.), but is the reflection of brain activation, that may be measured by the value of its dominating frequency? It is clear that this point of view does not rule out the involvement of the hippocampus in other specific functions.

2. Have you observed theta rhythm in any brain structures while it is absent in the hippocampus under different influences?

3. There is evidence that learning is provided by a high level of central tone that is formed through the mechanisms of temporary connections as a conditioned reflex of the first order according to P.S. Kupalov. Cannot it be considered on the basis of your findings that a prolonged maintenance of the necessary level of brain activation to a signaling stimulus under conditions of delay may occur thanks to the capacity of the hippocampal neural network to maintain excitation, that had earlier been established in clinical works and confirmed in great many experiments of the last time dealing with posttetanic potentiation?

T. Oniani. 1. Concerning the first question, I quite agree with you and think that no supplementary explanations and additions are required on my part.

2. In early 1970s in our laboratory it was established that except for the hippocampus the theta rhythm regularly develops in the entorhinal cortex (Oniani, T.N., Koridze, M.G., Kavkasidze, M.G., Gvetadze, L.B. The dynamics in excitability of various brain structures during different phases of wakefulness-sleep cycle. In: T.N. Oniani (Ed.), Neurophysiology of Emotion and Wakefulness-Sleep Cycle. Metsniereba, Tbilisi, 1974, I: 120-159 (in Russian)). In some cases during paradoxical sleep theta rhythm may appear in the visual area of the neocortex. The situations when the theta rhythm is absent in the hippocampus and develops in another structure have not been observed by us, provided, of course, the recording electrode is localised in the hippocampus, in the zone of development of theta rhythm and not in other layer wherein it is not generated.

3. At the present time there is convincing evidence indicating that the hippocampus by its descending influence may regulate activity of the mesodiencephalic structures which, apparently, are responsible for the occurrence of central tonic activity. There is no doubt that the optimally high level of central tonic activity provides good background for successful learning. It is quite possible that the hippocampus plays an important role in creating this optimal level of central tonic activity.

T. Radil. Prof. Oniani, my congratulations on the excellent report successfully analysing one of the most important questions of the functional and structural bases of conditioned reflex activity. You have demonstrated that during the hippocampal seizures there is cortical desynchronisation.

1. What are, in your opinion, other secondary changes occurring in different areas of the brain as a consequence of convulsive activity and postconvulsive depression of the hippocampus and in what way can they affect behavior?

2. How does the postconvulsive depression influence the pacemaker activity in the medial septum, i.e. would the theta rhythm generator stop or only its influence on the hippocampus is eliminated?

3. Have you tested the influence of pharmacological drugs (atropine, etc.) on the theta activity?

T. Oniani. 1. As I've demonstrated, against the background of local hippocampal epileptiform discharges electrical activity of the neocortex is desynchronised. We think it is the result of involvement in activity of the mesodiencephalic activating structures. At the repeated elicitation of hippocampal epileptiform discharges theta rhythm is suppressed, apparently, because of the disturbance of the pacemaker mechanism in the septum. Unfortunately, we have not made recording of activity from the septal pacemaker neurons against this background, that would have directly verified this assumption. Yet the fact that the pattern of slow wave sleep in postconvulsive period recovers much earlier than the theta rhythm in paradoxical sleep, speaks in favour of the above-said assumption.

2. Repeated epileptiform discharges cause considerable changes also in the sleep-wakefulness cycle, what no doubt indicate the alteration thereat of the functional state of the triggering mechanisms of different phases of this cycle. The more interesting is the fact that in spite of all this, repeated hippocampal epileptiform discharges do not induce retardation of learning, i.e. neither functional exclusion of the hippocampus in the consolidation phase of memory traces, nor arrest of development of the hippocampal theta rhythm prevent conversion of short-term memory into the long-term.

3. It is well known that atropine causes the abolishment of the hippocampal theta rhythm, but we have not used this vehicle, fearing that atropine could affect the cholinergic mechanisms of not only the septo-hippocampal system, but also of other systems of the brain, that would have made it rather difficult to assess the data obtained.

T.N. Sollertinskaia. 1. The hippocampus in mammals is not a homogeneous structure. What are your data and your opinion as to which areas of the hippocampus play a great role in the regulation of delayed responses?

2. There is a view advocated in its time by the school of Hungarian physiologists (Grastyan, Lissak and other) that the hippocampus plays an important role in regulating the processes of internal inhibition. What are your data and your opinion in the regulation of which processes of higher nervous activity is the hippocampus more involved?

3. Until the last time the question of a regulating role of the hippocampus in emotional reactions is disputable. Our data, obtained in a wide variety of vertebrates, testify that the role of the hippocampus in the regulation of emotional reactions is negligible. This is indicated also by the data of Meerson (a co-worker of our Institute) who has observed no changes in the emotional sphere of man after removal of the hippocampus. Have you observed any changes in emotional reactions after elimination of the hippocampus and what's your opinion on this point.

T. Oniani. 1. Neither the method of functional elimination of the hippocampus via elicitation in it of local epileptiform discharges, nor its partial deafferentation by means of lesion of the medial septum make it possible to judge about a specific role of one or another area of the hippocampus. We have demonstrated that even isolated lesion of the medial septum leads to the disturbance of delayed conditioned responses, i.e. short-term memory in "pure form" by Konorski is disturbed at this time. The same effect is observable also after the section of the entorhinal input to the hippocampus. Taking into account also the data known earlier one can conclude that any lesion of the basic limbic circuit results in a disturbance of short-term memory in "pure form".

2. Only on the basis of our own experiments I can say that the hippocampus plays an important role in regulating of short-term memory in "pure form", i.e. operative memory.

3. The role played by the hippocampus in the regulation of emotional reactions actually provokes a heated discussion, since the data obtained by different authors are rather discrepant. To refute the role played by the cortical structures in regulating of motivational-emotional reactions for that very reason that the triggering mechanisms for the given reactions are not represented there, is not right. The cortical structures of the limbic system serve as modulators of motivational-emotional reactions and their important role in this context consists namely in that.

L.A. Firsov. The first question is about the technique:

1. Had you to do with delayed responses of Hunter-Kerr type or delayed conditioned reflexes?

2. Aren't we engaged in tautology, speaking of learning and memory? The thing is that the process of learning per se is inseparable from the function of memory. May be we all will come to an agreement about intimate connection of the two processes (learning, storage or memory), but let us pose before us a task of evaluating the involvement of memory function in the process of skills organization.

T. Oniani. 1. In our experiments we have studied the effect of various manipulations on the delayed conditioned reflex reactions. This was stated by me in the methodical part of our experiments.

2. Of course, the process of learning is inseparably associated with the memory function, I do not understand, however, why you had the impression that I identify these notions. Although learning of any type (including the acquisition of a conditioned reflex) is underlined by memory, these are two notions, but, of course, not identical. I quite share the commonly accepted definitions of learning and memory: learning is the capability to change behavior under the influence of experience, while memory is the ability to retain these changes for some time. These definitions show well both the interrelationship between these phenomena and their distinctive features.

P. Milner. I should add my congratulations on the experiments revealing that theta rhythm is not obligatory for the consolidation and learning. I am interested in your opinion concerning the experiments of Bloch and coauthors, demonstrating that the rats show increase of paradoxical sleep after learning experiments compared to no-learning experiments.

T. Oniani. In the aspect of interaction of paradoxical sleep and learning we have made a systematic study of the effect of paradoxical sleep deprivation on learning, there was no effect. As to the effect of preliminary learning on the amount of paradoxical sleep in the sleep-wakefulness cycle following learning sessions, in this respect experiments are being carried out by us at present. On the basis of preliminary evidence I can say that the process of learning in alimentary tests has no considerable effect at all on the structure of the subsequent sleep-wakefulness cycle and on the amount of paradoxical sleep in the cycle, in particular. At the present time we specially breed kittens under conditions of social isolation in order to obtain a more or less "naive" brain where the interaction of learning and paradoxical sleep (if thus interaction does exist) could manifest itself better.

N.F. Suvorov. 1. In the report the difference was shown in the degree of disturbance of instrumental conditioned reflexes and delayed responses after functional elimination of the hippocampal theta rhythm or lesion of the lateral septum. There may be two kinds of explanation for these facts. Either the studied forms of behavior are differently difficult for the brain, or in delayed responses it is inhibition that functions to a greater extent, and it is known to be more labile, more vulnerable to any impacts on the organism.

2. You study the system of two subcortical structures, their involvement in the mechanisms of learning and memory. But in the integral behavior the subcortical structures always function with the neocortex. It is interesting to hear your opinion: with which areas of the cortex do the hippocampus and septum interact during the studied forms of behavior?

T. Oniani. 1. Thank you for the interesting statement on the importance of inhibition in the regulation of delayed responses.

2. It is logical to think that the hippocampus and septum both at motivational-emotional reactions and in learning tests are in closest interaction with the prefrontal neocortex, included the limbic system.

G. Abuladze. 1. It is known that the recurrent convulsive influences become less and less effective in respect of eliciting generalized seizures, amnesia, etc. Cannot this account for the inefficiency of electrical stimulation after each reinforcement in your experiments?

2. In the experiments on rats during elaboration of defense instrumental reactions we could not either observe the correlation of learning velocity or reproduction of active avoidance with theta rhythm of 4-7 Hz frequency. But this correlation was strong with a regular electrical activity of higher frequency (8-12 Hz). Have you got similar data?

T. Oniani. 1. If the electrical stimulation of the hippocampus, eliciting local epileptiform discharges, was applied immediately after a conditioned signal was reinforced with food, then there was an evident facilitation of learning. However, similar influence resulted in the disturbance of delayed responses to conditioned signals. So, in our experiments in both cases the effect was in evidence.

2. It seems to me that individual peculiarities in the theta rhythm frequency range may distinctly correlate with learning velocity. For example, animals with the optimally high level of the brain's nonspecific activation (B.I. Kotlyar rightfully refers to it as the central tone) will have theta rhythm within the high frequency range and would learn more easily than those with low nonspecific activation of the brain. Following lesion of the medial septum the hippocampal theta rhythm disappears in both groups of animals, but the differences in the levels of nonspecific activation of the brain and in learning velocity are maintained. Thus, the rate of learning depends on the level of nonspecific activation of the brain and not on the presence of the hippocampal theta rhythm of one or another frequency.

U.G. Gasanov. I would like to draw your attention to a particular methodical question in your work. It concerns the procedure of extinction. As far as I understand, you have made a chronic many-day extinction. At the same time the main object of investigation in conditioned reflex studies is an acute extinction during one experiment. It is just this form of extinction that shows exclusive sensitivity of an inhibitory process to various influences. In this relation I would like to ask you the following questions:

1. Why have you chosen the chronic form of extinction?

2. Can it be regarded that in your studies of food conditioned reflexes intervention into the function of the hippocampus is equally effective both for positive and inhibitory (extinguishing) conditioned reflex?

T. Oniani. 1. We studied the effect of septal lesion and evoked hippocampal epileptiform discharges both to acute and chronic extinction of instrumental alimentary reflexes. It could not have been otherwise, for in order to achieve a chronic extinction, several extinction sessions should be carried out, and in separate sessions one could well see namely the dynamics of acute extinction. So we had to do with both types of extinction.

2. The elaboration of extinction appears actually more sensitive to the influencing factors than that of a conditioned reflex.

V.L. Silakov. 1. How long have you studied delayed responses after the damage to the septal nuclei?

2. Could you notice any signs of compensation in the operated animals during observation?

3. Can the disturbed function of structures be compensated for at all?

T. Oniani. 1. Elaboration of instrumental alimentary reflexes in the cats with septal lesion was started after a complete recovery of the animal from the operational trauma in 8-12 days.

Extinction was made after stable discrimination of conditioned signals. All this took 1-1.5 months after surgery. As regards the delayed conditioned responses, deficit of which was observed in the postoperation period, they were tested for several months after surgery.

2. No restoration of delayed responses was observed during several months after the surgery.

3. The question of compensation of function of brain structures is so much obscure that I can hardly say anything helpful proceeding from the data reported by me.

P.V. Simonov. 1. First of all, I would like to point out the coincidence of your data with that demonstrated by me in the illustrations to my report: Functional elimination of the hippocampus as well as its damage affects the first stages of learning and has no effect on the stage of consolidation conditioned reflex. Intactness of the hippocampus is absolutely necessary for the elaboration of conditioned reflexes with a low probability of reinforcement, what, in a sense, coincides with your inference on the involvement of the hippocampus in the processes of short-term operative memory. Then there seems no discrepancy between your data and those of M.N. Livanov, H. Matties and other authors, which showed facilitation of elaboration of conditioned reflexes at the enhancement of theta rhythm through the stimulation of the septum. What do you think on this matter? How to say in purely neurophysiological aspect two consequences of elimination of the hippocampus: difficulty with the elaboration of a conditioned reflex and, simultaneously, facilitation of its extinction?

2. Wishing to assist with regarding the atmosphere of Gagra Talks, I would not label your report as "brilliant", "excellent", "logical", etc. (somehow earlier we had no use of such empty words), although it was very interesting for me to hear your speech.

T. Oniani. 1. I, too, noticed the coincidence of our findings with those reported by you. Concerning the facilitation of learning at the augmentation of theta rhythm in response to electrical stimulation of the septum, I want to say the following: expression of the hippocampal theta rhythm is distinctly correlated with the level of nonspecific activation of the brain within certain limits, the optimum level of nonspecific activation, the more readily proceeds learning. If at the electrical stimulation of the hippocampus the level of nonspecific activation of the brain increases, then it will entail both the facilitation of learning and the enhancement of the hippocampal theta rhythm. Of course, it does not mean that learning is facilitated because of the enhancement of the hippocampal theta rhythm, for similar ratio between the level of general activation of the brain and learning persists also after the lesion of medial septum, eliciting the removal of the hippocampal theta rhythm. At the extensive lesion of the septum, when, besides the medial, the lateral nucleus is also damaged, there is difficulty both with the extinction and elaboration of conditioned alimentary reflexes. This we explain by the development of the septal syndrome, which, apparently, is the result of the deficit of descending influence from the archipaleocortex.

The hippocampal theta rhythm did not appear to be the specific correlate of any behavioral act and of any step of memory organization, although the trials were great enough.

2. Your opinion concerning the theta rhythm reflecting primarily the process of inhibition of a pyramidal cells in the hippocampus is presently more and more convincingly confirmed in microelectric studies. The hypothesis that these inhibitory processes form gating mechanisms for information passage occurring along the cortical pathway is rather tempting. Only further experiments can show how much correct it is.

R.Yu. Ilyuchenok. Your data that the hippocampus does not determine the elaboration of a conditioned response is rather impressive. It's role is perhaps modulation. Therefore it's extremely interesting:

1. How many times was the preliminary habituation carried out?

2. May be the lack of effect was due to the removal of novelty of the experimental set?

3. The modulating role of the hippocampus apparently has a great significance in relation to the fixation of the trace to a new stimulus, while in relation to the elaboration of a conditioned response to a neutral stimulus the role of the hippocampus is not very essential. Following damage to the septum you have seen impairment of extinction, and this is the sign that the elaboration was going on to the stimulus from which novelty had been removed, does not the hippocampal lesion abolish the effect of latent suppression after habituation to the stimulus to which the response would be elaborated?

T. Oniani. 1. Experiments with the elaboration of conditioned instrumental alimentary reflexes were started after the cat for a few days had been adapted to the set in the experimental chamber. No preliminary habituation to conditioned signals was done, since the stimuli from the very beginning of experiments were new and then gradually acquired a concrete signaling value.

2. On the basis of our data one cannot speak about the lack of effect, since the massive lesion of the septum has a negative effect on the elaboration of conditioned reflexes. Similarly effective appears to be the retroactive functional elimination of the hippocampus that is particularly evident in the initial learning sessions. If the hippocampal epileptiform discharges were elicited for a short period after the delivery of conditioned signals then learning would be facilitated. Besides, both the lesion of the septum and epileptiform discharges affect most strongly the delayed conditioned responses.

A.M. Ivanitski. In ontogenesis the structures of the hippocampus mature earlier than the neocortex. It has been demonstrated that in this time period (that is between the maturation of the paleo- and neocortex) in rabbits only alimentary and not defence conditioned reflexes can be elaborated. In reptiles whose hippocampus is well developed, while the neocortex is represented only as a small band, removal of the hippocampus mostly affects the alimentary and not the defense reflexes. All this may suggest that the hippocampal structures are in some way related to the feeding behavior. What are your comments concerning this data from the point of view of your interesting conception on the functions of the hippocampus?

T. Oniani. During the development of the septal syndrome, which according to our data is mainly determined by the cessation of a descending influence from the archipaleocortex, there occurs hyperphagia. This indicates that the hippocampus and the other archipaleocortical structures somehow affect the food motivation. However with the septal syndrome there develops also aggressiveness and irritability. So that it is difficult to speak about the preferential role of the hippocampus in the regulation of feeding behavior.

E.N. Sokolov. The presented results suggest that the theta rhythm is not the necessary condition for learning. What are then the functions of theta rhythm? My explanation of this function boils down to the following. The theta rhythm is known to be represented by the neurons of the medial septum which are stimulated selectively in certain phases of theta rhythm (phase-specific neurons). The population of phase-specific neurons enables to fancy the separate moments of time after the action of a conditioned signal as specific neurons in relation to time. Thus, the population of phase-specific neurons enables to form a neuronal basis for time count. In other words, the neuronal population of the medial septum serves as a neuronal basis of the mechanism of abolition of conditioned reflexes.

T. Oniani. Thank you for the interesting comments.

N.Yu. Belenkov. 1. Is the elicitation of epileptiform discharges in the hippocampus an index of its functional elimination? May be the structure passes into another state?

2. Has the electroconvulsive activity of the hippocampus the effect only on the septum as a pacemaker of theta rhythm in the hippocampus or may be other structures of the limbic system and the rest of the brain are also affected?

3. You have demonstrated, in contrast to the existing opinion that the hippocampus plays no crucial role in the formation of long-term memory. Do not your findings confirm the point of view, including mine, that for the realization of the function of long-term memory there are no critical structures?

T. Oniani. 1. That the epileptiform discharges cause the functional elimination in that cortical structure wherein they arise, is beyond any doubt. Of course, at this time the structure passes from one state at which its coordinated activity is accomplished, into another at which the coordinating activity of the structure is disturbed. Namely this is the functional elimination.

2. In my report I presented the evidence that the hippocampal epileptiform discharges, apart from disturbing activity of the theta rhythm pacemaker, elicit changes in the functional state of the mesodiencephalic structures. By this we explain the described changes in learning velocity.

3. As far as I know yet there is no evidence indicating that any structure of the brain is a depot of traces of long-term memory.

R. Ray. Despite Dr. Simonov's disclaimer about our use of compliments, I liked very much the conceptual strategies your paper represents for studying the role of hippocampal theta and memory. And I congratulate you on a very interesting paper.

However, I have a methodological question. In the presentation of your conditioning results you have shown us the quantified and summarized data for all the subjects in each group, and have indicated their statistical reliability for differences between conditions.

On the other hand, for the hippocampal data we were shown only a brief, and presumedly representative, recording sample of the raw data. There is growing evidence from laboratories working on spectral quantification of electroencephalographic data that visual inspection of such data gives totally different characterization of the data than do quantitative techniques. It seems very difficult for humans to do a successful Fourier analysis of complex wave forms by the eye. Thus it is not obvious to me that your epileptic periods involve less theta, but only that they include a great deal more of a high-powered and high-frequency oscillation. Are you suggesting that results should be interpreted only in relative terms or do you fell quantification of absolute power is most important to consider in determining whether theta or theta-suppression is important in memory?

T. Oniani. Thank you for the congratulations. As to the fragments of records of the hippocampal theta rhythm, I have presented them, first, to show in which phase of the sleep-wakefulness cycle this activity is most pronounced, and secondly, in order to show how the hippocampal electrical activity alters following lesion of the medial septum. The first case shows a quantitative change of theta rhythm, and the second, qualitative change of electrohippocampogram. After lesion of the medial septum the hippocamapal theta rhythm disappears altogether, because of the absence of its pacemaker. In this case no quantitative methods are required for the measurement of the hippocampal theta rhythm. I would like to emphasize here one circumstance: when we speak of the hippocampal theta rhythm, we, as well as others, imply a regular activity of slow waves within the range 4-8 Hz per sec (in the cat), and not the irregular potentials which by their duration may fall into the range of theta rhythm and which may arise also after the lesion of the theta rhythm pacemaker, localized in the medial septum, for example, during slow wave sleep. In other cases (for example, while studying the effect of recurrent epileptiform discharges of the hippocampus, when the theta rhythm pacemaker is intact, but its functional state is seldom decreased) qualitative analysis is made by all means. In particular, we studied the frequency-amplitude characteristics of theta rhythm and found sharp quantitative changes before its depression. As was demonstrated, similar changes of theta rhythm result in no significant delay in learning.

All these facts brings us to the conclusion that the development of the hippocampal theta rhythm per se is not an important factor for the consolidation of memory traces during elaborating instrumental alimentary reflexes.

T. Naneishvili. Does not exclusion of the possibility of theta rhythm generation indicate the functional elimination of the hippocampus? May be it would be more reasonable to speak about the exclusion of that neuronal organization of the hippocampus at which theta rhythm is generated?

T. Oniani. For the functional elimination of the hippocampus we employed the method of eliciting in it of epileptiform discharges. Ruling out the possibility of reproduction of theta rhythm cannot, of course, be considered as the functional elimination of the hippocampus. Thus, for example, lesion of the medial septum leads to a complete abolishment of the hippocampal theta rhythm, but one cannot speak of a complete functional elimination of this structure, for the hippocampus may receive messages through other inputs and exert influence through the outputs on the related to it structures. Suppression of theta rhythm is observed for rather a long time after multiple elicitation of the hippocampal epileptiform discharges, but I do not think that at this time there is also the functional elimination of the hippocampus. Perhaps at this time there occurs a disturbance of functioning of the theta rhythm pacemaker on the level of the medial septum.

L.L. Voronin. 1. Didn't you make an attempt to calculate the correlation between the amplitude (or any other index of theta rhythm) and learning in norm and at various experimental interventions?

2. Have you compared the effects of epileptiform stimulation of the hippocampus with analogous control stimulation of other structures at the elaboration of ordinary and delayed conditioned responses?

3. Had the stimulation of the hippocampus any effect on the elaboration of an ordinary conditioned reflex during its application in the interval between the conditioned and unconditioned stimuli (or immediately after a conditioned stimulus)?

T. Oniani. 1. As been stated above, one of the cogent arguments presented in favor of the significance of the hippocampal theta rhythm in the consolidation of memory traces often is the fact that in animals with the pronounced theta rhythm learning proceeds faster than in those with poorly expressed theta rhythm. However, if in both groups of animals apply lesion to the medial septum and thereby remove the hippocampal theta rhythm, then the difference in learning velocity persists. Persists because both the expression of the hippocampal theta rhythm and the velocity of learning are dependent on the level of the nonspecific activation of the brain. There is no direct relation between the learning velocity and the expression of the hippocampal theta rhythm.

2. We have not studied the effect of epileptiform discharges of other brain structures on learning velocity and delayed reactions.

3. If the hippocampal epileptiform discharges are elicited immediately after the delivery of a conditioned signal, then there occurs disturbance of delayed responses. We have not studied the effect of a similar influence on the elaboration of conditioned response. In learning sessions the hippocampal epileptiform discharges were elicited after the combination of conditioned and unconditioned stimuli.

F. Klingber. Prof. Oniani, your extremely interesting and accurate experiments and results provide nutrition for the discussion of many questions. Here are two of them.

1. Is the slow hippocampal activity correlated with the orientation reflex? It is clear that the orientation response is not abolished after lesion of the medial septum. This complex response contains various components, tonic and phasic, which do not depend on the septo-hippocampal input. The slow hippocampal rhythm was observed by us not only during the orientation response, but always, whenever the animal was attentive and performed the so-called nonautomatic acts. Later on Vanderwolf named them "voluntary movements", but we do not agree to such terminology. More suitable is the hypothesis of Buzhak and Grastyan who refer to such behavior as "auto-shaping". We know now that the main inputs through the medial septum are cholinergic and noradrenergic. The majority of these inputs are inhibitory. In 1966, in the laboratory of Schtumpf, it was found by us that more and more pyramidal neurons of field CA1 of the anterior pole of the dorsal hippocampus are inhibited with an increase of frequency of the hippocampal slow rhythm. In my opinion, the hippocampal slow rhythm reflects the gating mechanism of the hippocampus. What do you think about this?

2. This question is similar to that of Simonov. Is the hippocampus important for memory consolidation? Most of the data from the laboratory of Maties indicate that it is. Even in the framework of the theory of Milner of the cellular pool we can hardly deny this. A concrete question - what form of memory? What is consolidated? I suppose all the most important information from the cortex arrives through the perforant pathway and that this information is processed along the circuit of Papez, which, apparently is the most important structure for learning with low probability. The septal input has an important gating function and primarily the noradrenergic fibres should play a role in the increase of the signal level over noise. Do you share this hypothesis?

T. Oniani. 1. The regular slow hippocampal activity (in the range of theta rhythm in cats and in certain conditions reaching 8-12 Hz in rats) may serve as an electrographic correlate for many behavioral acts, requiring for their performance the enhancement of nonspecific activity of the brain. Such acts are: the orientation reaction, fear, aggression, food-procuring activity, conditioned reflex movements, etc. Rhythmic activity of the hippocampus may arise also without any evident motor acts, in case the emotional tension of the animal reaches a certain level. The regular synchronized activity of the hippocampus appears to be most pronounced during paradoxical sleep. Recording of neuronal activity from the mesodiencephalic structures indicates that it is just at this time that enhancement of nonspecific activity of the brain occurs. Assumption of Green and Arduini that the level of development of the hippocampal theta rhythm corresponds to that of arousal is perhaps more right. The hippocampal theta rhythm is so much vividly expressed and readily measurable event that it always attracted attention of investigators of the neurophysiological mechanisms of behavior. They all considered that the hippocampal theta rhythm is causally related with the reactions investigated by them. Actually, all these reactions are realized on the background of nonspecific activation of the brain and, respectively, there occurs the enhancement of the hippocampal theta rhythm. The hippocampal theta rhythm is not a specific correlate for any behavioral act or any level of memory organization, although there were and still are many an attempt made to prove this.

2. Usually, by the term "consolidation" one means delivery of traces of short-term memory to a long-term storage. The same meaning was construed by us too speaking of the role played by the hippocampus in the processes of consolidation of memory traces. On the basis of the results obtained we cannot conclude that the processes directly related with the consolidation of memory traces occur in the hippocampus.

The major information arrives in the hippocampus not only through the perforant, but also through the rather vigorous septal input, which, as you have rightly noticed, has an important gating function. Perhaps the information, having arrived in the hippocampus, is transferred for storage to other structures of the limbic circuit, integrity of which is rather important for learning in general, and not only for the learning with low probability. For the realization of a gating function of the septum great importance have the cholinergic, and not only adrenergic fibres of the medial forebrain bundle.