- Email: [email protected]
Hippocampal Slow Wave Activity as a Correlate of Basic Behavioral Mechanisms in the Rat
218
Hippocampal Slow Wave Activity as a Correlate of Basic Behavioral Mechanisms in the Rat L. PI CKE NHAI N
AND
F. KLINGBERG
Department of Clinical Neurophysiology, Neurological-PsychiatricClinic, Karl-Marx University, Leipzig (German Democratic Republic)
Since the occurrence of a regular slow wave activity in the hippocampus of the cat was described and interpreted as an accompaniment of arousal by Green and Arduini in 1954 many investigations have been carried out to clear up the correlation between different behavioral states and the appearance of this characteristic hippocampal activity. But whereas many details of the eliciting trigger mechanism of the slow hippocampal rhythm (SHR) have been described in the work of Brucke et al. (1959 a,b) and Petsche et al. (1962), up to now no agreement on the relation of this rhythm to special behavioral elements in the animal has been reached. There is only agreement that such a correlation exists, but how is not clear. Grastyhn et al. (1959) and Lisshk and Grastyhn (1960) assume that the SHR is in correlation with an orienting activity of the animal. They found it regularly in the early phase of conditioning in which orienting reactions play an important role, and they observed that its occurrence decreased and iinally ceased completely if the conditioned reflex was M y established. Adey et al. (1960) deny an immediate connection between the SHR and the orienting reflex because they frequently observed head movements without the concomitant appearance of the SHR. They suppose that it is connected with a goal-directed behavior of the animal. In well-established conditioned motor reflexes in cats they did not observe the disappearance of the SHR as Grastyhn et al. did in their experiments. Finally Voronin and Kotljar (1962, 1963), who elaborated instrumental conditioned alimentary reflexes in rabbits, distinguished between a slow form of the SHR (6-8/sec), which is supposed to be connected with the orienting reflex, and a fast form (&lO/sec) being an expression of a ‘synthesis of different nervous stages elicited by the signal, the movement and the unconditioned stimulus’. AU these interpretations are based on experimental observations and are confirmed by many other authors, but it seems that a theoretical scheme is lacking to combine the different behavioral and electrophysiological observations. During the last three years we carried out combined electrophysiologicaland behavioral studies in more than 70 awake, freely moving rats with chronically implanted electrodes (Klingberg and Pickenhain, 1964; Pickenhain and Klingberg, 1965). The
HIPPOCAMPAL SLOW W A V E ACTIVITY
219
electrodes were located in different cortical areas, in the dorsal hippocampus, in the antero-ventral thalamus and occasionally in other subcortical regions. Concomitantly with the EEGs the respiration (by means of electrodes placed near the olfactory bulb) and the motor activity (with the help of a method described by Szab6 et al., 1965) were recorded. During the whole experiment the behavior of the rat was recorded by the experimenter. Different behavioral states were evoked by means of clicks or light flashes given separately or in series, by different familiar or unfamiliar stimuli and by the elaboration and succeeding extinction of avoidance, aversive or alimentary conditioned reflexes. During these experiments we obtained extensive material on the relationship between the SHR and the behavior of the rat. In rats the frequency range of the SHR is higher than in cats. The lowest frequency with which the neurones in the dorsal hippocampus of the rat can follow the triggering salvos from the medial septa1 cells is 6/sec. Under special conditions this frequency can rise to 12/sec. This frequency range is the same as reported on rabbits (Sailer and Stumpf, 1957). We will try to answer two questions. (1) In what behavior situations can we observe the slow hippocampal rhythm? and (2) What is the dynamics of the frequency pattern of the slow regular rhythm in the dorsal hippocampus compared with the concomitant behavioral acts? Not every arousal is accompanied by the SHR. Fig. 1 shows that an arousal is elicited by a click. The animal displays a strong startle reaction (recorded on line M), and the electrographic pattern in the cortical derivations and in the dorsal hippocampus changes from a highly synchronized sleeping pattern into a desynchronized waking pattern. The startle reflex is not followed by any orienting motor reaction. In the derivation from the dorsal hippocampus (DH) one sees a high-frequency low-voltage activity. We confirm the statement of Grastyhn et al. (1959) that the SHR is not a necessary accompaniment of arousal nor of the startle reflex. In accord with these authors we found that a new stimulus which bears for the animal no resemblance to former stimuli does not elicit the SHR. In Fig. 2 we give another example, in which the click (mark on line S) is followed by an arousal without eliciting a startle reflex. As in Fig. 1, the DH displays a low amplitude irregular activity, but 4 sec later a slow regular rhythm sets in. Simultaneously one observes a stronger desynchronization in the cortical derivations and in the antero-ventral thalamus. Half a second later the animal performs an orienting movement (on line M) lasting about 1.5 sec. After this time the SHR (in DH) and the orienting movements (in M) disappear simultaneously, and 1 sec later in all cortical and subcortical derivations the sleeping pattern of the electrical activity reappears. Note that the SHR (in DH) sets in before the overt orienting motor activity is observed. Fig. 3 represents an example in which the animal performs an orienting reaction elicited by a noise in the experimental room. One can see the occurrence of the slow regular rhythm in the DH correlated with the orienting motor activity (M) and an acceleration of respiration (R).During its best representation in the DH the SHR is transferred to the visual cortex, a phenomenon often observed in the rat. The References p . 227
220
L. P I C K E N H A I N A N D F. KLINGBERG
Fig. 1. Electrographic arousal in rat to a click. VC = visual cortex; DH = dorsal hippocampus; TH = antero-ventral thalamus; MC = sensori-motor cortex; AC = auditory cortex; R = respiration; M = motor activity. In M one can see a strong startle reflex. Calibrations:horizontal, 1 sec; vertical, 200 pV.
frequency and amplitude of the SHR decrease during a transitory motor silence, bur they show a new increase with a new strengthening of the orienting motor activity. In our experiments with rats we regularly observed this occurrence of the SHR during the orienting motor activity. The essential feature of all these situations consisted in the fact, that the eliciting stimulation bore information that was in some respect similar to the formerly received information. Like Grastyh el al. (1964), we saw neither an orienting reaction nor the SHR if the stimulation was completely new for the animal. In this event, after repeated applications, the stimulus acquired the property of eliciting these two reactions. Therefore, we can characterize the behavioral situation in which the SHR appears as one in which the animal compares the actual sensory information coming from the situation with previously stored information. The statement, that stimuli given the first time do not elicit the orienting motor reaction or the SHR, is also valid if strong nociceptive stimuli are applied. An example appears in Fig. 4. The single lines represent the derivation from the DH
HIPPOCAMPAL SLOW W A V E A C T I V I T Y
22 1
Fig. 2. Electrographic and behavioral arousal in rat to a click. S = signal mark; T = time, 1 sec. Calibration, 200 pV. The orienting motor reaction (M) is preceded by the appearance of the slow regular rhythm in the dorsal hippocampus @H) and concomitant stronger desynchronization in the other cortical and subcortical derivations.
during the first, second, etc. . . . application of I0 short, strong eIectrica1 stimuli, marked on the top line. During the first applications of the electrical stimulus series from the grid floor no SHR was observed, although the animal exerted chaotic efforts to escape. With the following applications the occurrence of the SHR increased gradually until it occupied not only the period of stimulation but also a great part of the interstimulus period (stimulations 10 and 16). With the 16th stimulus series the animal displayed the first successful avoidance reaction, jumping from the grid floor to a freely moving rod. What happens during this time in the brain of the animal? To the first electrical stimuli, which were completely unexpected, the animal displayed different inco-ordinated motor reactions such as jerking around in the cage, biting the bars of the grid floor, jumping against the cage walls and so on. During the interstimulus period an arresting behavior predominated. With further applications of the stimulus series an orienting behavior prevailed more and more, and the most appropriate elements of the chaotic motor acts were selected and gradually combined to a new, well-adapted behavior. Finally, immediately after the first electrical stimulus of the series, the rat jumped on to the rod and avoided further electrical shocks. Apparently in this experiment the SHR was correlated not only with the orienting motor reactions, but also with the dynamic process of forming the new, well-adapted motor behavior. Essentially in the same way the SHR develops during the elaboration of a condiReferences ~ - 2 2 7
222
L. P I C K E N H A I N A N D F. K L I N G B E R G
Fig. 3. Orienting reaction elicited by a noise in the experimental room. Concomitantly with the orienting motor reaction one can see the appearanceof the slow hippocampal rhythm in DH and VC, and the acceleration of respiration. Abbreviations and calibrations as in Figs. 1 and 2.
tioned reflex. This process was described in detail by Grastybn et al. (1959) who pointed out that the orienting motor reaction plays an important role during the early stage of conditioning. But let us take an example of a later stage when the animal displays a well-adapted conditioned avoidance behavior. Fig. 5 represents such an example. The rat, having received more than 50 combinations of a series of 10 light flashes followed by an electrical shock from the grid floor, now displays a stable avoidance reflex (jumping on to a rod). With the first light flash one can see the appearance of the SHR without any motor reaction or acceleration of respiration. The amplitude and frequency of the SHR decrease, and, as a sign of the inhibited behavior of the animal, photic after-discharges in the visual cortex appear 700 msec later. This is a regular phenomenon in the first, so-called negative, phase of a delayed conditioned reflex. About 2 sec later the SHR again increases in frequency and amplitude, the respiration accelerates, and after the 5th flash the animal displaysa slight movement directed to the rod. Immediately before the jump (marked by an arrow) the SHR has a frequency maximum; immediately after the animal hangs on the rod, both frequency and amplitude decrease. The question arises whether here too the SHR is an expression of an orienting reaction. We think not. Behaviorally, after the first flash the animal exerts no motor components of any orienting reaction, and the respiration also shows no significant acceleration. The motor reaction after the 5th flash is apparently not an accompaniment of an orienting reaction but of a goal-directed behavior, clearly motivated by the whole situation. We think it would overcharge the term ‘orienting behavior’ to use it
HIPPOCAMPAL SLOW WAVE ACTIVITY
223
Fig. 4. Derivation from dorsal hippocampus in the rat during successive (1st. . 16th) applications of sets of 10 strong electrical shocks from the grid floor. The line at the top marks single electrical shocks. During the 16th shock series the rat jumps (arrow) to a freely hanging rod, thus avoiding further shocks. Calibration: horizontal, 1 sec; vertical, 200 pV.
in this connection. We prefer to describe this situation by saying that the animal compares actual sensory information with formerly stored information in order to perform certain well-adapted actions. This comparison is valid as long as the motor behavior has not yet changed into an automatized behavior. This change of the motivated motor behavior into automatized motor acts depends on the special experimental conditions. Therefore, Holmes and Adey (1 960) and Sadowski and Longo (1962) did not observe the disappearance of the SHR in the period of stabilized conditioned reflexes in cats, whereas GrastyLn et al. (1959) saw it. Voronin and Kotljar (1963) observed the SHR in rabbits even after 800 combinations of conditioned and unconditioned stimuli, and we observed the same in rats after more than 200 combinations. This also applies when we use alimentary conditioning. In Fig. 6 we show a ‘spontaneous’ intersignalreaction of a rat that had a stabilized alimentary motor conditioned reflex. The rat was sitting quietly at its starting place and began suddenly to run to the food tray (arrow upward). This motivated motor act began with an SHR whose frequency and amplitude increase during running. After the animal arrived at the feeding place, it displayed some sniffing motions during which the SHR disappeared, References p . 227
224
I.. P I C K E N H A I N A N D F. K L I N G B E R G
Fig. 5. Electrogram from the visual cortex (VC), sensori-motorcertex (MC) and dorsalhippocampus OH), respiration (R) and motor activity (M)during a conditioned avoidancereflex in rat. On line S: marks, single light flashes; arrow, conditioned jump on to the rod. Calibrations: horizontal, 1 sec; vertid, 200 pV.
Fig. 6. Interstimulus reaction during conditioned motor alimentary behavior in rat. VC1 and VCZ, visual cortex, bipolar and unipolar; DH1 and DHa, dorsal hippocampus, bipolar and unipolar; Th. antero-ventral thalamus; R, respiration;M,motor activity; S, arrow upward, beginning of running; arrow downward, beginning of drinking. Calibrations: horizontal, 1 sec; vertical 200 pV.
H I P P O C A M P A L SLOW WAVE ACTIVITY
225
Fig. 7. Conditioned motor alimentary reaction in rat. On line S: marks of light flashes; the downward mark after the 5th light flash, unlocking of the door; arrow upward, beginning of running; arrow downward, beginning of drinking. Calibrations as for Fig. 6.
and after this it began to drink (arrow downward). During the automatized motor act of licking the glucose solution no SHR was observed. Therefore, in this example, too, we can say that the occurrence of the SHR is correlated with a motivated, nonautomatized motor behavior of the rat. The strong correlation between non-automatized motor behavior and SHR on the one hand, and automatized motor behavior and lack of SHR on the other hand are shown in Fig. 7. During the interstimulus period the animal exhibits an SHR owing to the motivated alimentary situation. But as soon as the rat begins to scratch (recorded on line M) the SHR disappears, and in spite of the beginning of the conditioned stimuli it does not return as long as the scratching is continued. Only after the 4th flash, when scratching has finished, does the SHR appear again in a very marked manner, and the animal turns its head to the door through which it must pass to reach the food. But the SHR ceases again because the door is unlocked only between the 5th and 6th flashes (at the downward mark). After this the animal runs quickly to the food tray (arrow upward) and begins to drink (arrow downward). During drinking no SHR is observed. Reviewing our experimental facts we can answer our first question in the following way. The SHR in the dorsal hippocampus appears in all behavioral situations in which the rat displays a motivated behavior. This motivated behavior may include motivated, non-automatized motor acts, or it may be an inhibited motivated behavior as in the first, inhibited period of the conditioned reaction of Fig. 5. In these latter examples one can assume that the animal directs its attention to the changing situation and prepares motivated motor acts. Inversely, all motor acts of the rat are accompanied by the occurrence of the SHR if they are motivated, and if they are not References p . 227
226
L. P I C K E N H A I N A N D P. KLINGBERG
automatized. In other terms one can say that the SHR appears in all situationsin which a comparison of the actual sensory information with formerly storedinformation takes place. This likewise happens during the so-called orienting or searching behavior as when the animal elaborates a new, well-adapted motor behavior using inborn or formerly acquired elementary behavioral acts. During the performance of a welladapted routine the SHR only appears, if the performance of the motor acts is not automatized and further on requires slightly changing, subtle variations of the adapted motor acts. This interpretation of the SHR as an expression of a dynamic comparator mechanism fits well both with former assumptions on the mechanism of the orienting behavior (Sokolov, 1963) and with the concept that the structure of the hippocampus is appropriate for the comparisonof signalsof differentmodalities (McLardy, 1959). As to the second question we have already mentioned that the frequency of the SHR in the rat changes from 6/sec to 12/sec. These frequency changes also show a clear correlation with the animal's behavior. The frequency range lies between 6 and
Fig. 8. Derivations from antero-ventralthalamus (TH), visual cortex (VC)and dorsal hippocampus (DH), respiration (R) and motor activity (M) of a rat when the experimenter suddenly pulls the rod, which the animal touches with its forepaws, out of the cage (arrow).Calibrationsas in Fig. 6.
8/sec if the animal displays no or only slight motivated movements, and it increases up to 12/sec if it shows strongly excited, motivated or goal-directed motor acts. In Fig. 8 the experimenter pulls the rod, which the rat touches with its forepaws, suddenly out of the cage. Immediately, in the dorsal hippocampus a SHR appears with maximal frequency (12fsec) and maximal amplitude, the respiration accelerates, and the animal displays very strong orienting motor reactions. But the rat quickly calms down displaying only slight searching movements, and the SHR decreases both in frequency (6-7/sec) and amplitude. Therefore, we assume that the frequency range of the SHR is correlated with the amount of central activation during motivated behavior. As Sailer and Stumpf
H I P P O C A M P A L SLOW W A V E A C T I V I T Y
227
( 1957) showed in rabbits, in which they stimulated the lateral hypothalamus, a stronger
stimulation gives a higher frequency of the SHR, ranging up to 12/sec. One can assume that this is also valid in the animal that is awake during the influence of natural stimuli. The amount of impulses coming from the lateral hypothalamus and reaching the medial septa1cells determines the frequency of the SHR during motivated behakior. REFERENCES ADEY,W. R., DUNLOP, C. W.,
AND
HENDRIX,C. E., (1960); Hippocampal slow waves. Arch. Neuroi.
(Chic.), 3, 74-90. BRUCKE,F., PETSCHE,H., PILLAT,B.,
UND DEISENHAMMER, E., (1959a); Die Beeinflussung der ‘Hippocampus-arousal-Reaktion’beim Kaninchen durch elektrische Reizung im Septum. Pfiigers
Arch. ges. Physiol., 269, 319-338.
BRUCKE,F., PETSCHE, H., PILLAT,B., UND DEISENHAMMER, E., (1959b); a e r Veranderungen des Hippocampus-Elektroencephalogrammes beim Kaninchen nach Novocaininjektion in die Septumregion. Naunyn-Schmiedeberg’s Arch. exp. Path. Pharmk., 237, 276-284. GRASTY~N, E., (1959); The hippocampus and higher nervous activity. The Central Nervous System and Behaviour, M. A. B. Brazier, Editor. Transactions of the Second Conference. Macy Found., New York, pp. 119-205. GRASTYAN, E., KARMOS, G., VERECZKEY, L., UND LOSONCZY, H V., (1964); Uber den nervalen Mechanismus des Orientierungsreflexes. Wis.2.Karl-Marx-Univ. Leipzig, Math. Naturw. Reihe, 13, 1169-1 174.
GRASTY~N, E., LISSAK,K., M A D A R ~ I., Z , AND DONHOFFER, H., (1959); HipFocampal electrical activity during the development of conditioned reflexes. Electroenceph. din. Neurophysiol., 11, 409430.
GREEN, J. D.,
17, 533-557.
AND
ARDUINI, A., (1954); Hippocampal electrical activity in arousal. J. Neurophysiol.,
HOLMES, J. E., AND ADEY,W. R., (1960); Electricalactivity oftheentorhinalcortex during conditioned behaviour. Amer. J. Physiol., 199, 741-744. KLINGBERG, F., UND PICKENHAIN, L., (1964); Veranderungen des ECG, der kortikalen hervorgerufenen Potentiale und der Startle-Reaktionen bei Ratten wahrend der Ausarbeitung eines bedingten Fluchtreflexes. Acta biol. med. germ., 12, 552-567. L I S S ~ KK., , AND GRASTY~N, E., (1960); The changes of hippocampal electrical activity during conditioning. Moscow Colloquium on Electroencephalography of Higher Nervous Activity. H. H. Jasper and G, D. Smirnov, Editors. Electroenceph. clin. Neurophysiol., Suppl. 13, 271-279. MCLARDY, T., (1959); Hippocampal formation of brain as detector-coder of temporal patterns of information. Perspect. Biol. Med., 2, 443-452. F’ETSCHE, H., STUMPF, CH., AND GOGOLAK, G., (1962); The significance of the rabbit’s septum as a relay station between the midbrain and the hippocampus. I. The control of hippocampal arousal activity by the septum cells. Electroenceph. clin. Neurophysiol., 14, 202-21 1. PICKENHAIN, L. AND KLINGBERG, F., (1965); Behavioural and electrophysiological changes during avoidance conditioning to light flashes in rat. Electroenceph. elin. Neurophysiol., 18,464476. SADOWSKI, B., AND LONGO,V. G., (1962); Electroencephalographic and behavioural correlates of an instrumental reward conditioned response in rabbits, a physiological and pharmacological study. Electroenceph. clin. Neurophysiol., 14,465-476. SAILER, S., UND STUMPF, CH., (1957) ;Beeinflussbarkeit der rhinenzephalen Tatigkeit des Kaninchens. Naunyn-Schmiedeberg’s Arch. exp. Pathol. Pharmak., 231, 63-77.
SOKOLOV, E. N., (1963); Orienting reflex as cybernetic system. Zh. vyssh. nerv. Deyat., Pavlova, 13,
8 16-830. Szm6, I., KELL~NYI, L., AND KARMOS, G., (1965); A simple device for recording movements of unrestrained animals. Actaphysiol. Acnd. Sci. hung., 26, 343-349. VORONIN, L. G., AND KOTLJAR,B. I., (1962); Bioelectrical activity of some parts of the brain during elaboration and extinction of alimentary conditioned reflex. Zh. vyssh. nerv. Deyat., Pavlova, 12, 547-554. (Russian) L. G., AND KOTUAR,B. I., (1963); Cortical electrical activity during formation and stabiliVORONIN, zation of alimentary and avoidance motor conditioned reflexes. Zh. vyssh. nerv. Deyat. Pavlova, 13, 917-927. (Russian)
Hippocampal Slow Wave Activity as a Correlate of Basic Behavioral Mechanisms in the Rat L. PI CKE NHAI N
AND
F. KLINGBERG
Department of Clinical Neurophysiology, Neurological-PsychiatricClinic, Karl-Marx University, Leipzig (German Democratic Republic)
Since the occurrence of a regular slow wave activity in the hippocampus of the cat was described and interpreted as an accompaniment of arousal by Green and Arduini in 1954 many investigations have been carried out to clear up the correlation between different behavioral states and the appearance of this characteristic hippocampal activity. But whereas many details of the eliciting trigger mechanism of the slow hippocampal rhythm (SHR) have been described in the work of Brucke et al. (1959 a,b) and Petsche et al. (1962), up to now no agreement on the relation of this rhythm to special behavioral elements in the animal has been reached. There is only agreement that such a correlation exists, but how is not clear. Grastyhn et al. (1959) and Lisshk and Grastyhn (1960) assume that the SHR is in correlation with an orienting activity of the animal. They found it regularly in the early phase of conditioning in which orienting reactions play an important role, and they observed that its occurrence decreased and iinally ceased completely if the conditioned reflex was M y established. Adey et al. (1960) deny an immediate connection between the SHR and the orienting reflex because they frequently observed head movements without the concomitant appearance of the SHR. They suppose that it is connected with a goal-directed behavior of the animal. In well-established conditioned motor reflexes in cats they did not observe the disappearance of the SHR as Grastyhn et al. did in their experiments. Finally Voronin and Kotljar (1962, 1963), who elaborated instrumental conditioned alimentary reflexes in rabbits, distinguished between a slow form of the SHR (6-8/sec), which is supposed to be connected with the orienting reflex, and a fast form (&lO/sec) being an expression of a ‘synthesis of different nervous stages elicited by the signal, the movement and the unconditioned stimulus’. AU these interpretations are based on experimental observations and are confirmed by many other authors, but it seems that a theoretical scheme is lacking to combine the different behavioral and electrophysiological observations. During the last three years we carried out combined electrophysiologicaland behavioral studies in more than 70 awake, freely moving rats with chronically implanted electrodes (Klingberg and Pickenhain, 1964; Pickenhain and Klingberg, 1965). The
HIPPOCAMPAL SLOW W A V E ACTIVITY
219
electrodes were located in different cortical areas, in the dorsal hippocampus, in the antero-ventral thalamus and occasionally in other subcortical regions. Concomitantly with the EEGs the respiration (by means of electrodes placed near the olfactory bulb) and the motor activity (with the help of a method described by Szab6 et al., 1965) were recorded. During the whole experiment the behavior of the rat was recorded by the experimenter. Different behavioral states were evoked by means of clicks or light flashes given separately or in series, by different familiar or unfamiliar stimuli and by the elaboration and succeeding extinction of avoidance, aversive or alimentary conditioned reflexes. During these experiments we obtained extensive material on the relationship between the SHR and the behavior of the rat. In rats the frequency range of the SHR is higher than in cats. The lowest frequency with which the neurones in the dorsal hippocampus of the rat can follow the triggering salvos from the medial septa1 cells is 6/sec. Under special conditions this frequency can rise to 12/sec. This frequency range is the same as reported on rabbits (Sailer and Stumpf, 1957). We will try to answer two questions. (1) In what behavior situations can we observe the slow hippocampal rhythm? and (2) What is the dynamics of the frequency pattern of the slow regular rhythm in the dorsal hippocampus compared with the concomitant behavioral acts? Not every arousal is accompanied by the SHR. Fig. 1 shows that an arousal is elicited by a click. The animal displays a strong startle reaction (recorded on line M), and the electrographic pattern in the cortical derivations and in the dorsal hippocampus changes from a highly synchronized sleeping pattern into a desynchronized waking pattern. The startle reflex is not followed by any orienting motor reaction. In the derivation from the dorsal hippocampus (DH) one sees a high-frequency low-voltage activity. We confirm the statement of Grastyhn et al. (1959) that the SHR is not a necessary accompaniment of arousal nor of the startle reflex. In accord with these authors we found that a new stimulus which bears for the animal no resemblance to former stimuli does not elicit the SHR. In Fig. 2 we give another example, in which the click (mark on line S) is followed by an arousal without eliciting a startle reflex. As in Fig. 1, the DH displays a low amplitude irregular activity, but 4 sec later a slow regular rhythm sets in. Simultaneously one observes a stronger desynchronization in the cortical derivations and in the antero-ventral thalamus. Half a second later the animal performs an orienting movement (on line M) lasting about 1.5 sec. After this time the SHR (in DH) and the orienting movements (in M) disappear simultaneously, and 1 sec later in all cortical and subcortical derivations the sleeping pattern of the electrical activity reappears. Note that the SHR (in DH) sets in before the overt orienting motor activity is observed. Fig. 3 represents an example in which the animal performs an orienting reaction elicited by a noise in the experimental room. One can see the occurrence of the slow regular rhythm in the DH correlated with the orienting motor activity (M) and an acceleration of respiration (R).During its best representation in the DH the SHR is transferred to the visual cortex, a phenomenon often observed in the rat. The References p . 227
220
L. P I C K E N H A I N A N D F. KLINGBERG
Fig. 1. Electrographic arousal in rat to a click. VC = visual cortex; DH = dorsal hippocampus; TH = antero-ventral thalamus; MC = sensori-motor cortex; AC = auditory cortex; R = respiration; M = motor activity. In M one can see a strong startle reflex. Calibrations:horizontal, 1 sec; vertical, 200 pV.
frequency and amplitude of the SHR decrease during a transitory motor silence, bur they show a new increase with a new strengthening of the orienting motor activity. In our experiments with rats we regularly observed this occurrence of the SHR during the orienting motor activity. The essential feature of all these situations consisted in the fact, that the eliciting stimulation bore information that was in some respect similar to the formerly received information. Like Grastyh el al. (1964), we saw neither an orienting reaction nor the SHR if the stimulation was completely new for the animal. In this event, after repeated applications, the stimulus acquired the property of eliciting these two reactions. Therefore, we can characterize the behavioral situation in which the SHR appears as one in which the animal compares the actual sensory information coming from the situation with previously stored information. The statement, that stimuli given the first time do not elicit the orienting motor reaction or the SHR, is also valid if strong nociceptive stimuli are applied. An example appears in Fig. 4. The single lines represent the derivation from the DH
HIPPOCAMPAL SLOW W A V E A C T I V I T Y
22 1
Fig. 2. Electrographic and behavioral arousal in rat to a click. S = signal mark; T = time, 1 sec. Calibration, 200 pV. The orienting motor reaction (M) is preceded by the appearance of the slow regular rhythm in the dorsal hippocampus @H) and concomitant stronger desynchronization in the other cortical and subcortical derivations.
during the first, second, etc. . . . application of I0 short, strong eIectrica1 stimuli, marked on the top line. During the first applications of the electrical stimulus series from the grid floor no SHR was observed, although the animal exerted chaotic efforts to escape. With the following applications the occurrence of the SHR increased gradually until it occupied not only the period of stimulation but also a great part of the interstimulus period (stimulations 10 and 16). With the 16th stimulus series the animal displayed the first successful avoidance reaction, jumping from the grid floor to a freely moving rod. What happens during this time in the brain of the animal? To the first electrical stimuli, which were completely unexpected, the animal displayed different inco-ordinated motor reactions such as jerking around in the cage, biting the bars of the grid floor, jumping against the cage walls and so on. During the interstimulus period an arresting behavior predominated. With further applications of the stimulus series an orienting behavior prevailed more and more, and the most appropriate elements of the chaotic motor acts were selected and gradually combined to a new, well-adapted behavior. Finally, immediately after the first electrical stimulus of the series, the rat jumped on to the rod and avoided further electrical shocks. Apparently in this experiment the SHR was correlated not only with the orienting motor reactions, but also with the dynamic process of forming the new, well-adapted motor behavior. Essentially in the same way the SHR develops during the elaboration of a condiReferences ~ - 2 2 7
222
L. P I C K E N H A I N A N D F. K L I N G B E R G
Fig. 3. Orienting reaction elicited by a noise in the experimental room. Concomitantly with the orienting motor reaction one can see the appearanceof the slow hippocampal rhythm in DH and VC, and the acceleration of respiration. Abbreviations and calibrations as in Figs. 1 and 2.
tioned reflex. This process was described in detail by Grastybn et al. (1959) who pointed out that the orienting motor reaction plays an important role during the early stage of conditioning. But let us take an example of a later stage when the animal displays a well-adapted conditioned avoidance behavior. Fig. 5 represents such an example. The rat, having received more than 50 combinations of a series of 10 light flashes followed by an electrical shock from the grid floor, now displays a stable avoidance reflex (jumping on to a rod). With the first light flash one can see the appearance of the SHR without any motor reaction or acceleration of respiration. The amplitude and frequency of the SHR decrease, and, as a sign of the inhibited behavior of the animal, photic after-discharges in the visual cortex appear 700 msec later. This is a regular phenomenon in the first, so-called negative, phase of a delayed conditioned reflex. About 2 sec later the SHR again increases in frequency and amplitude, the respiration accelerates, and after the 5th flash the animal displaysa slight movement directed to the rod. Immediately before the jump (marked by an arrow) the SHR has a frequency maximum; immediately after the animal hangs on the rod, both frequency and amplitude decrease. The question arises whether here too the SHR is an expression of an orienting reaction. We think not. Behaviorally, after the first flash the animal exerts no motor components of any orienting reaction, and the respiration also shows no significant acceleration. The motor reaction after the 5th flash is apparently not an accompaniment of an orienting reaction but of a goal-directed behavior, clearly motivated by the whole situation. We think it would overcharge the term ‘orienting behavior’ to use it
HIPPOCAMPAL SLOW WAVE ACTIVITY
223
Fig. 4. Derivation from dorsal hippocampus in the rat during successive (1st. . 16th) applications of sets of 10 strong electrical shocks from the grid floor. The line at the top marks single electrical shocks. During the 16th shock series the rat jumps (arrow) to a freely hanging rod, thus avoiding further shocks. Calibration: horizontal, 1 sec; vertical, 200 pV.
in this connection. We prefer to describe this situation by saying that the animal compares actual sensory information with formerly stored information in order to perform certain well-adapted actions. This comparison is valid as long as the motor behavior has not yet changed into an automatized behavior. This change of the motivated motor behavior into automatized motor acts depends on the special experimental conditions. Therefore, Holmes and Adey (1 960) and Sadowski and Longo (1962) did not observe the disappearance of the SHR in the period of stabilized conditioned reflexes in cats, whereas GrastyLn et al. (1959) saw it. Voronin and Kotljar (1963) observed the SHR in rabbits even after 800 combinations of conditioned and unconditioned stimuli, and we observed the same in rats after more than 200 combinations. This also applies when we use alimentary conditioning. In Fig. 6 we show a ‘spontaneous’ intersignalreaction of a rat that had a stabilized alimentary motor conditioned reflex. The rat was sitting quietly at its starting place and began suddenly to run to the food tray (arrow upward). This motivated motor act began with an SHR whose frequency and amplitude increase during running. After the animal arrived at the feeding place, it displayed some sniffing motions during which the SHR disappeared, References p . 227
224
I.. P I C K E N H A I N A N D F. K L I N G B E R G
Fig. 5. Electrogram from the visual cortex (VC), sensori-motorcertex (MC) and dorsalhippocampus OH), respiration (R) and motor activity (M)during a conditioned avoidancereflex in rat. On line S: marks, single light flashes; arrow, conditioned jump on to the rod. Calibrations: horizontal, 1 sec; vertid, 200 pV.
Fig. 6. Interstimulus reaction during conditioned motor alimentary behavior in rat. VC1 and VCZ, visual cortex, bipolar and unipolar; DH1 and DHa, dorsal hippocampus, bipolar and unipolar; Th. antero-ventral thalamus; R, respiration;M,motor activity; S, arrow upward, beginning of running; arrow downward, beginning of drinking. Calibrations: horizontal, 1 sec; vertical 200 pV.
H I P P O C A M P A L SLOW WAVE ACTIVITY
225
Fig. 7. Conditioned motor alimentary reaction in rat. On line S: marks of light flashes; the downward mark after the 5th light flash, unlocking of the door; arrow upward, beginning of running; arrow downward, beginning of drinking. Calibrations as for Fig. 6.
and after this it began to drink (arrow downward). During the automatized motor act of licking the glucose solution no SHR was observed. Therefore, in this example, too, we can say that the occurrence of the SHR is correlated with a motivated, nonautomatized motor behavior of the rat. The strong correlation between non-automatized motor behavior and SHR on the one hand, and automatized motor behavior and lack of SHR on the other hand are shown in Fig. 7. During the interstimulus period the animal exhibits an SHR owing to the motivated alimentary situation. But as soon as the rat begins to scratch (recorded on line M) the SHR disappears, and in spite of the beginning of the conditioned stimuli it does not return as long as the scratching is continued. Only after the 4th flash, when scratching has finished, does the SHR appear again in a very marked manner, and the animal turns its head to the door through which it must pass to reach the food. But the SHR ceases again because the door is unlocked only between the 5th and 6th flashes (at the downward mark). After this the animal runs quickly to the food tray (arrow upward) and begins to drink (arrow downward). During drinking no SHR is observed. Reviewing our experimental facts we can answer our first question in the following way. The SHR in the dorsal hippocampus appears in all behavioral situations in which the rat displays a motivated behavior. This motivated behavior may include motivated, non-automatized motor acts, or it may be an inhibited motivated behavior as in the first, inhibited period of the conditioned reaction of Fig. 5. In these latter examples one can assume that the animal directs its attention to the changing situation and prepares motivated motor acts. Inversely, all motor acts of the rat are accompanied by the occurrence of the SHR if they are motivated, and if they are not References p . 227
226
L. P I C K E N H A I N A N D P. KLINGBERG
automatized. In other terms one can say that the SHR appears in all situationsin which a comparison of the actual sensory information with formerly storedinformation takes place. This likewise happens during the so-called orienting or searching behavior as when the animal elaborates a new, well-adapted motor behavior using inborn or formerly acquired elementary behavioral acts. During the performance of a welladapted routine the SHR only appears, if the performance of the motor acts is not automatized and further on requires slightly changing, subtle variations of the adapted motor acts. This interpretation of the SHR as an expression of a dynamic comparator mechanism fits well both with former assumptions on the mechanism of the orienting behavior (Sokolov, 1963) and with the concept that the structure of the hippocampus is appropriate for the comparisonof signalsof differentmodalities (McLardy, 1959). As to the second question we have already mentioned that the frequency of the SHR in the rat changes from 6/sec to 12/sec. These frequency changes also show a clear correlation with the animal's behavior. The frequency range lies between 6 and
Fig. 8. Derivations from antero-ventralthalamus (TH), visual cortex (VC)and dorsal hippocampus (DH), respiration (R) and motor activity (M) of a rat when the experimenter suddenly pulls the rod, which the animal touches with its forepaws, out of the cage (arrow).Calibrationsas in Fig. 6.
8/sec if the animal displays no or only slight motivated movements, and it increases up to 12/sec if it shows strongly excited, motivated or goal-directed motor acts. In Fig. 8 the experimenter pulls the rod, which the rat touches with its forepaws, suddenly out of the cage. Immediately, in the dorsal hippocampus a SHR appears with maximal frequency (12fsec) and maximal amplitude, the respiration accelerates, and the animal displays very strong orienting motor reactions. But the rat quickly calms down displaying only slight searching movements, and the SHR decreases both in frequency (6-7/sec) and amplitude. Therefore, we assume that the frequency range of the SHR is correlated with the amount of central activation during motivated behavior. As Sailer and Stumpf
H I P P O C A M P A L SLOW W A V E A C T I V I T Y
227
( 1957) showed in rabbits, in which they stimulated the lateral hypothalamus, a stronger
stimulation gives a higher frequency of the SHR, ranging up to 12/sec. One can assume that this is also valid in the animal that is awake during the influence of natural stimuli. The amount of impulses coming from the lateral hypothalamus and reaching the medial septa1cells determines the frequency of the SHR during motivated behakior. REFERENCES ADEY,W. R., DUNLOP, C. W.,
AND
HENDRIX,C. E., (1960); Hippocampal slow waves. Arch. Neuroi.
(Chic.), 3, 74-90. BRUCKE,F., PETSCHE,H., PILLAT,B.,
UND DEISENHAMMER, E., (1959a); Die Beeinflussung der ‘Hippocampus-arousal-Reaktion’beim Kaninchen durch elektrische Reizung im Septum. Pfiigers
Arch. ges. Physiol., 269, 319-338.
BRUCKE,F., PETSCHE, H., PILLAT,B., UND DEISENHAMMER, E., (1959b); a e r Veranderungen des Hippocampus-Elektroencephalogrammes beim Kaninchen nach Novocaininjektion in die Septumregion. Naunyn-Schmiedeberg’s Arch. exp. Path. Pharmk., 237, 276-284. GRASTY~N, E., (1959); The hippocampus and higher nervous activity. The Central Nervous System and Behaviour, M. A. B. Brazier, Editor. Transactions of the Second Conference. Macy Found., New York, pp. 119-205. GRASTYAN, E., KARMOS, G., VERECZKEY, L., UND LOSONCZY, H V., (1964); Uber den nervalen Mechanismus des Orientierungsreflexes. Wis.2.Karl-Marx-Univ. Leipzig, Math. Naturw. Reihe, 13, 1169-1 174.
GRASTY~N, E., LISSAK,K., M A D A R ~ I., Z , AND DONHOFFER, H., (1959); HipFocampal electrical activity during the development of conditioned reflexes. Electroenceph. din. Neurophysiol., 11, 409430.
GREEN, J. D.,
17, 533-557.
AND
ARDUINI, A., (1954); Hippocampal electrical activity in arousal. J. Neurophysiol.,
HOLMES, J. E., AND ADEY,W. R., (1960); Electricalactivity oftheentorhinalcortex during conditioned behaviour. Amer. J. Physiol., 199, 741-744. KLINGBERG, F., UND PICKENHAIN, L., (1964); Veranderungen des ECG, der kortikalen hervorgerufenen Potentiale und der Startle-Reaktionen bei Ratten wahrend der Ausarbeitung eines bedingten Fluchtreflexes. Acta biol. med. germ., 12, 552-567. L I S S ~ KK., , AND GRASTY~N, E., (1960); The changes of hippocampal electrical activity during conditioning. Moscow Colloquium on Electroencephalography of Higher Nervous Activity. H. H. Jasper and G, D. Smirnov, Editors. Electroenceph. clin. Neurophysiol., Suppl. 13, 271-279. MCLARDY, T., (1959); Hippocampal formation of brain as detector-coder of temporal patterns of information. Perspect. Biol. Med., 2, 443-452. F’ETSCHE, H., STUMPF, CH., AND GOGOLAK, G., (1962); The significance of the rabbit’s septum as a relay station between the midbrain and the hippocampus. I. The control of hippocampal arousal activity by the septum cells. Electroenceph. clin. Neurophysiol., 14, 202-21 1. PICKENHAIN, L. AND KLINGBERG, F., (1965); Behavioural and electrophysiological changes during avoidance conditioning to light flashes in rat. Electroenceph. elin. Neurophysiol., 18,464476. SADOWSKI, B., AND LONGO,V. G., (1962); Electroencephalographic and behavioural correlates of an instrumental reward conditioned response in rabbits, a physiological and pharmacological study. Electroenceph. clin. Neurophysiol., 14,465-476. SAILER, S., UND STUMPF, CH., (1957) ;Beeinflussbarkeit der rhinenzephalen Tatigkeit des Kaninchens. Naunyn-Schmiedeberg’s Arch. exp. Pathol. Pharmak., 231, 63-77.
SOKOLOV, E. N., (1963); Orienting reflex as cybernetic system. Zh. vyssh. nerv. Deyat., Pavlova, 13,
8 16-830. Szm6, I., KELL~NYI, L., AND KARMOS, G., (1965); A simple device for recording movements of unrestrained animals. Actaphysiol. Acnd. Sci. hung., 26, 343-349. VORONIN, L. G., AND KOTLJAR,B. I., (1962); Bioelectrical activity of some parts of the brain during elaboration and extinction of alimentary conditioned reflex. Zh. vyssh. nerv. Deyat., Pavlova, 12, 547-554. (Russian) L. G., AND KOTUAR,B. I., (1963); Cortical electrical activity during formation and stabiliVORONIN, zation of alimentary and avoidance motor conditioned reflexes. Zh. vyssh. nerv. Deyat. Pavlova, 13, 917-927. (Russian)