Sleep pattern of hippocampectomized cat

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SLEEP P A T T E R N OF H I P P O C A M P E C T O M I Z E D CAT

CHUL KIM, HYUN CHOI, JONG KYU KIM, MYUNG SUK KIM, MAN KYUNG HUH AND YUNG BEEN MOON Department of Physiology, Catholic Medical College, Seoul (Korea) (Accepted January Ist, 1971)

INTRODUCTION In the course of observing the occurrence of components of general behavioral activity by a time-sampling method, this laboratory has recently observed significantly reduced sleep incidence in hippocampectomized rats 15. Though a few studies have implicated the hippocampus in the sleep mechanism 10,2°,21, hitherto the hippocampus has more often been correlated with fast-wave sleep2,a,5,tl, 25 than with slow-wave sleep, perhaps because of the dominant theta waves appearing in the hippocampus during fast-wave sleep. The present study was designed to see whether sleep reduction in hippocampectomized animals observed in this laboratory can be confirmed electrophysiologically by recording, in cats, the EEG, E M G and electrooculogram (EOG) before and after removal of the hippocampus; and if so, whether slow-wave sleep, fast-wave sleep, or both phases of sleep are affected by hippocampectomy. MATERIALSAND METHODS Subjects Twenty-two male cats were used (mean body weight, 3.35 kg; range, 2.5-4.1 kg). They were subjected to experiment after adaptation to the laboratory environment for at least 1 week. Su~e~ Pentobarbital sodium (30 mg/kg body wt.) was used to anesthetize the animals, and aseptic precautions were taken. Electrode implantation. In the exposed skull, two elliptical holes (major axis, around 3 mm, minor axis 1 mm) were made, one about 3 mm to the right of the sagittal suture and 12 mm caudal to the coronal suture, and the other about 8 mm to the left of the sagittal suture and 5 mm caudal to the coronal suture. Through each hole, Brain Research, 29 (1971) 223-236

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a pair of silver electrodes with circular tips at right angles with the shaft (tip diameter, 1.5 ram; distance between two tips, 2 mm) was implanted epidurally and fixed to the skull with acrylic dental cement. These electrodes recorded the EEG from the marginal gyrus and suprasylvian gyrus, respectively. Another pair of silver electrodes for E M G was implanted in the nuchal muscles. In addition, a unipolar silver electrode, anchored in the connective tissue over the external ocular muscles, picked up the EOG between this and an indifferent electrode fixed to the sagittal crest. Free ends of all electrodes were soldered to a miniature connector fixed to the skull with screws and dental cement. Removal ofhippocampal and cortical tissues. A round hole with a diameter about 6 mm was made in each parietal bone about 1.25 cm lateral to the sagittal suture and 1.7 cm caudal to the coronal suture. After the dura had been excised, the exposed cortical tissue on each side was removed, and then as much of the hippocampal tissue as possible was sucked out bilaterally, using a No. 18 gauge suction tip. Care was taken not to damage the neighboring brain structures. This preparation served as the hippocampectomized animal. Cats assigned for cortical lesion alone received the same surgery short of hippocampal ablation. For one week after surgery, penicillin G 100,000 units, and streptomycin 0.125 g/kg body weight were administered intramuscularly to prevent infection. Apparatus During EEG, E M G and EOG recording, each animal was accommodated in a sound-attenuated wooden box (inner dimensions, 50 cm × 60 cm × 50 cm) with a transparent front wall. A 10 W lamp lighted the interior of the box (12 Lux) throughout the recording session, so that the behavior of the animal could be observed and compared with the EEG, E M G and EOG tracings at any time. The temperature inside the box was kept at 22-24°C, and the noise level at 3 4 4 0 dB in the daytime and 33-34 dB at night (measured by a sound level meter, Rion type NA-D8, A-weighted). The recording room was illuminated with a fluorescent lamp (7 Lux) from 8. a.m. to 8 p.m. Procedure Each animal had a control recording session about 2 weeks after electrode implantation. The animal was put in the sound-attenuated box at 6 p.m. on the day before the recording session began. Electrodes were connected to a polygraph (Schwarzer type PEE 8) by means of a plug with leads, and the animal was allowed to adapt itself to the new environment. Food and water were always available. The control recording session began at 8 a.m. on the next morning with a polygraph paper speed of 2.5 mm/sec and continued for 24 h. When the control recording session was over, the animals were randomly subjected either to hippocampectomy (11 animals) or to cortical lesion (11 animals). After 3 weeks rest, each animal had an experimental recording session in the same condition as in the control recording session. Three of the cortical animals received Brain Research, 29 (1971) 223-236

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hippocampectomy immediately after the experimental recording session was over. These animals had a third recording session 3 weeks later.

Collection and analysis of data The sleep phase with synchronized cortical electrical activity and reduced muscular tonus was regarded as slow-wave sleep (SWS), and the sleep phase with cortical desynchronization, muscular atony and rapid eye movement as fast-wave sleep (FWS). From the records, SWS, FWS and sleep state (defined as a sequence of SWS or SWS-FWS phases between two successive waking states) were measured in terms of their occurrence (i.e., SWS occurrence, FWS occurrence and sleep state occurrence), mean duration (mean SWS duration, mean FWS duration, and mean sleep state duration) and the total time occupied by them (total SWS time, total FWS time and total sleep time) in the daytime, at night and in 24 h. Control results obtained from 22 cats were pooled. The experimental data obtained from 11 hippocampectomized animals and data obtained in the third recording session from the 3 cortical cats that received hippocampectomy later were also pooled. Data gathered were analyzed statistically (by the t test, Mann-Whitney U test, or Wilcoxon test) the level of significance being set at 5 ~o.

Histological findings Upon completion of the experiments, each animal received an overdose of pentobarbital sodium. The brain was perfused with saline followed by 10 ~o formalin, frozen and sectioned frontally at 50 #m. Around 20 informative sections from each brain showing the lesions were photographed at × 4 with an enlarger. The extent of hippocampal damage was estimated by each of 3 independent observers and expressed as a percentage of total tissue bulk. Sections through the brain of a hippocampectomized cat are illustrated in Fig. 1. Both in the cortical and hippocampal animals, the cortical lesion was a round one with a diameter of about 6 mm situated in each posterior ectosylvian-suprasylvian junctional cortex (PES cortex). No apparent subcortical damage was found in the brains of cortical animals. In 14 cats that underwent ablation of the hippocampus, an average of 96.4 ~o of the latter structure was removed. One brain with the least hippocampal damage retained about 15 ~o of that structure, and 4 brains had no hippocampal tissue. Most brains retained less than 4--5 ~ of the hippocampal tissue almost always in the ventral portion of that structure lying between the mammillary and tuberal levels and abutting on the subiculum. The ventral hippocampal tissue remained bilaterally in 4 cats and unilaterally in 6 cats. Rarely, fragments of dorsal hippocampal tissue remained beneath the corpus callosum. Besides the hippocampus, slight unilateral tissue damage was found occasionally in the thalamus, the amygdaloid nucleus, and the pyriform cortex. The thalamic lesions included single cases of superficial damage along the ventrolateral surface of

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Fig. 1. Coronal sections through the brain of a hippocampectomized cat. See also next page.

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Brain Research, 29 (1971) 223-236

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Experimental

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Hippocampal ( N = 14)

S, sequence comprising only o n e S W S p h a s e ; 1-2S, s e q u e n c e s c o m p r i s i n g f r o m S W S - F W S to S W S - F W S - S W S - F W S - S W S ; 3 or m o r e alternating S W S a n d F W S phases. A n u m e r a l to t h e right o f e a c h asterisk is larger t h a n t h e P value.

SLEEP TIME, SLEEP OCCURRENCE, MEAN SLEEP DURATION, AND FREQUENCY OF SLEEP SEQUENCES IN DAYTIME, AT NIGHT AND IN 24 H

TABLE I

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24 h Daytime Night 24h Daytime Night 24 h Daytime Night

61.4 36.6 24.8 27.9 14.1 13.8 10.9 4.0 6.9

4- 23.4 d= 5.7 **.°-°1 4- 10.4 4- 7.7 4- 5.3 ± 5.3 4- 6.8 4- 3.2 ***°'°l ± 4.6

6.5 4- 1.2 6.5 ± 1.7 6.5 4- 1.2

74.8 4- 9.4 *o.0o06 40.4 4- 10.0 34.4 -1= 8.2 *0.o04 18.9 4- 8.1 *°'°1 8 . 0 ± 3.1 *0.05 10.9 4- 7.8 6.7 4- 4.2 *0.05 2.9 4- 2.5 3.8 4- 3.3 *°'°a

6.2 4- 1.0 5.6 ~ 1.3 6.8 4- 1.2

* The value is significantly different from the control value (t test, Mann-Whitney U). ** The value is significantly different from the cortical experimental value (t test, Mann-Whitney U). *** The value is significantly different from that recorded at night (t test, Witcoxon).

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82.6 49.6 33.0 13.1 5.2 7.9 3.8 1.0 2.8

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7.4,0.00o6, **0.02 8.6,0.003, ***o.ol

5.5 ± 12 *0.05 4.5 4- 2.4,o.ol, ***0.05 6.54- 2.0

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Fig. 2. Minute-by-minute shifts between wakefulness (W), SWS (S), and FWS (F) observed in hippocampal experimental (HE), cortical experimental (CE), and control (C) sessions in a cat. the medial geniculate body, along the dorsal surface of the nucleus reticularis or nucleus lateralis dorsalis, and 2 cases of a small round perforating lesion in the white matter ventrolateral to the lateral geniculate body. The lesion of the amygdaloid nucleus included 2 cases of superficial damage along the medial surface facing the optic tract, and a case where a portion of the tissue juxtaposed to the anteroventral extremity of the hippocampus was slightly involved. The pyriform cortex was perforated in one case close to the subiculum. The corpus callosum between cortical lesions was frequently involved in the damage. Data obtained from preparations that had much remaining hippocampal tissue or showed manifest damage to other subcortical structures such as thalamus, septum or amygdaloid nucleus were discarded. RESULTS

Data on sleep time, sleep occurrence and duration as well as sleep sequence are summarized in Table I, and an example of minute-by-minute shifts between wakefulness, SWS and FWS is diagrammatically illustrated in Fig. 2. Sleep time

In Table I, the total sleep time, total SWS time and total FWS time in a 24 h Brain Research, 29 (1971) 223-236

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period are expressed as percentages of total observation time. There was no significant change in total sleep time in 24 h as a result of cortical damage, but significant reduction in the value after hippocampectomy (P < 0.001, t test). The total sleep time of the hippocampectomized cats was also considerably less than that of the cortically lesioned animals (P < 0.01). The same trend was apparent with regard to the total SWS time in 24 h; the hippocampal experimental value was significantly reduced compared both with the control value (P < 0.01) and the cortical experimental value (P < 0.01), while the latter 2 values did not differ much from each other. The cortical damage reduced the total FWS time in 24 h significantly (P < 0.01). Hippocampectomy resulted in more significant reduction in the total FWS time (P < 0.001), but the 2 experimental values did not differ significantly.

Sleep occurrence Sleep state occurred in 24 h neither more nor less often after cortical damage, but significantly more often after hippocampectomy (P < 0.001). It occurred in the hippocampectomized cat more often than in the cortical animals (P < 0.001). Analysis also showed significantly increased occurrence in 24 h of the SWS phase after hippocampectomy (P < 0.001) but not after cortical lesion, the 2 experimental values being significantly different (P < 0.001). The FWS phase occurred significantly less often after cortical damage (P < 0.02) as well as after hippocampectomy (P < 0.001), the difference between the 2 experimental values not being significant.

Sleep duration The mean durations (in min) of both the sleep state and the SWS phase observed in a 24 h period were not affected by cortical lesion, but were significantly reduced as a result of hippocampectomy (duration of sleep state, P < 0.001 ; duration of SWS phase, P < 0.001), and the values after hippocampectomy differed considerably from those following cortical damage (duration of sleep state, P < 0.001 ; duration of SWS phase, P < 0.001). The mean duration of the FWS phase observed in a 24 h period was reduced nonsignificantly after cortical damage, but significantly after hippocampectomy (P < 0.05), the 2 experimental values not being significantly different from each other.

Sleep sequence The frequencies of occurrence of each sleep sequence (SWS, SWS-FWS, SWSFWS-SWS, etc.) expressed as percentage of total sleep sequence occurrences in 24 h are plotted in Fig. 3. After brain lesions, the sleep sequence including only one SWS phase increased at the cost of those comprising more of the SWS and FWS phases. In Table I, the data are grouped into 3 classes to facilitate statistical comparison. The first class contains the sequence comprising only one SWS phase. This sequence, the most frequently encountered in the control period as well as after brain damages,

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Fig. 3. Frequency of occurrence of each sleep sequence expressed as percentage of total sleep sequences during 24 h. S, 1, IS, etc. denotes a sleep sequence including only one SWS phase, a sequence including one SWS-FWS pair, and a sequence including SWS-FWS-SWS phases etc,, respectively. significantly increased after cortical damage (P < 0.006, Mann-Whitney U) and also after hippocampectomy (P < 0.00006), the increment being considerably more conspicuous after hippocampectomy than after cortical lesion (P < 0.02). The occurrence of sleep sequences grouped in the second class (from SWS-FWS to S W S - F W S - S W S FWS-SWS) was significantly decreased as a result of cortical damage (P < 0.01) as well as after removal of the hippocampus (P < 0.00006); the value after hippocampectomy was significantly less than the value after cortical lesion (P < 0.05). The occurrence of sleep sequences grouped in the third class (sequences including 3 or more alternating SWS and FWS phases) also showed the same trend; the value decreased significantly after cortical damage (P < 0.05) and more seriously after hippocampectomy (P < 0.001) though the difference between the 2 experimental values did not reach statistical significance. Circadian variation in sleep

In Table I, the day and the night values on sleep are included. A significant day versus night difference existed with regard to the total sleep time, total SWS time, and

total FWS time under normal conditions, after cortical damage, and also following hippocampectomy, except that after cortical lesion the day versus night difference of the total SWS time fell short of significance. With regard to sleep occurrence and sleep duration, no consistent day versus night difference of significance existed even under normal conditions. However, all values on sleep, which showed a significant day versus night difference under normal conditions, showed the same difference after hippocampectomy. Therefore the circadian variation was well preserved after hippocampectomy. Changes in FWS after hippocampectomy tended to be more conspicuous in the daytime than at night (cf. Table I). Thus the total FWS time of the hippocampal Brain Research, 29 (1971) 223-236

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animals decreased markedly in the daytime (P < 0.001, t test) but less prominently at night (P < 0.02) compared with the corresponding control values. In the hippocampectomized animal, the FWS occurred significantly less often in the daytime (P < 0.001), but almost as often at night as it occurred in the control period. Also the mean FWS duration of the hippocampal group was significantly reduced in the daytime (P < 0.01), but not at all at night compared with the control values. Such a trend was not apparent in the cortical animals. DISCUSSION

According to the present investigation, normal cats under our laboratory conditions spent 55.5% of the time in SWS, 13.9% in FWS, and 30.7% in the awake state. The data are in agreement with those obtained by Sterman et aL 27 whose cats spent 14.4 ~ o f the time in a drowsy state, 42.2 % in spindle burst sleep, 15.5 % in FWS, and 28 % in the awake state. The drowsy state together with the spindle burst sleep of their animals correspond to our SWS. FWS occurred 32.2 times a day in our cats, and 31.5 times in cats studied by Ursin 80. The circadian rhythm of sleep after hippocampectomy was preserved as distinctly as in normal conditions. However, the total sleep time and the total SWS time in a 24 h period were significantly reduced, the occurrences of sleep state and SWS phase in the same period were increased and the mean duration of the sleep state and SWS phase were all reduced significantly after removal of the hippocampus, but not after cortical lesion alone. The cause of increase in the occurrence of the sleep state and SWS phase against their reduced duration is not clear, but it may represent an activity of the central sleep mechanism to compensate for deficient sleep. With regard to FWS, a cortical lesion alone reduced both the total FWS time and the occurrence of FWS significantly. Removal of the hippocampus tended to reduce these values more significantly, but there were no reliable differences between the 2 experimental values. The results induce doubt as to whether the hippocampus has anything to do with the FWS. However, it was after hippocampectomy, but not after cortical lesion, that the mean duration of FWS was significantly reduced and that the reductions in the total FWS time, in the occurrence of FWS as well as in the mean duration of FWS, were all much more pronounced in the daytime than at night, when the noise level was low. Working with cats in which afferent fibers to the hippocampus had been interrupted at the septal level but their cerebral cortex was intact, Lena and Parmeggiani 16 noted a significant reduction in the occurrence and total time spent in FWS in a noisy environment, a finding that we corroborate. These observations do not prove, but seem to suggest the involvement of the hippocampus in the FWS phase of sleep. From the results of the present study, it may be inferred that the hippocampus takes part in the sleep mechanism as a regulator facilitating maintenance of sleep. The results are in line with those of stimulation of the fornix in man producing reduced consciousnessla, 26 and of stimulation of the hippocampus in animals yielding behavior preparatory to sleep2°, 21, actual falling into sleep 24, hastened appearance of fast-wave Brain Research,

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sleep 6, or at least no arousal in sleeping animals 17. The results are also in agreement with our recent lesion study using rats 15 and with the work done by Jarrard ~° whose hippocampectomized rats spent less time in sleep than did control rats. However, the present results do not exclude a possibility of the hippocampus also being involved in the arousal mechanism. Actually, the attention of animals was frequently invoked upon stimulation of the hippocampus~, ~s. Hernandez-Pe6n s included the hippocampus in his cholinergic arousal system. Working with monkeys, Votaw zl reported that stimulation of the middle third of the cornu Ammonis caused a general arousal response, whereas ablation of the same structure produced a lethargic animal. There may exist different or even opposing functional systems separated spatially or mingled in one and the same hippocampal tissue1,7,28, zg. Thus it may be more appropriate to speak of the hippocampus as a mechanism predominantly conducive to the maintenance of sleep. The present results offer but little suggestion as to how the hippocampus works and where its influence is exerted in facilitating sleep. Parmeggiani 22 proposed a working hypothesis that the hippocampal output during the theta rhythm - - which would occur in FWS as well as in arousal - - exerts a synchronizing influence on the activity of subcortical and neocortical neurons and therefore counteracts the desynchronizing effects of the reticular activating system. However, we have seen that the hippocampus exerts a definite influence upon the SWS phase, when there is no theta rhythm at all. Therefore the hippocampus may exert its influence upon the sleep mechanism through the theta rhythm as well as through other unidentified means, be it a tonic or a feedback activity. With regard to the locus or loci upon which the hippocampal influence is exerted, suffice it to say that there may be several candidates including the brain stem reticular formation, hypothalamus 19, and thalamus 9, and that recently Clemente and Sterman 4 described a basal forebrain sleep mechanism, of which the hippocampus was a link in its efferent path. It would be appropriate to add a few words on the FWS phase. In this study, a small lesion in the PES cortex significantly reduced the occurrence of FWS as well as the total FWS time in a 24 h period. According to Woolsey 32, there are in the suprasylvian and the posterior ectosylvian gyri areas responding to auditory stimulus with 15 msec and 100 msec latencies. As the FWS seems to be especially susceptible to noise ~4, the damaged cortex may be involved in the regulation of FWS in response to auditory impulse. But it is not clear how the PES cortex works and whether it is under the influence of the hippocampus 23. SUMMARY

To see whether the hippocampus has any influence upon the sleep mechanism, 11 male cats that had more than 90 ~ of their hippocampal tissue removed bilaterally through an opening in each posterior ectosylvian-suprasylvian junctional cortex (PES cortex) and 11 animals that received the same surgery short of hippocampectomy were prepared. Their EEG, E M G and E O G were recorded for 24 h before and after damage to the brain. F r o m the records, slow-wave sleep (SWS), fast-wave sleep Brain Research, 29 (1971) 223-236

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(FWS) and sleep state (defined as a sequence o f SWS or S W S - F W S phases between two successive awake states) were measured in terms o f their occurrence, mean duration and the total time they occupied in the observation period. PES cortical damage did not affect the sleep state or SWS phase with regard to their occurrence, mean duration and total time they occupied in 24 h, but produced a significant reduction in F W S occurrence and in total F W S time. H i p p o c a m p e c t o m y significantly reduced the total time occupied by the sleep state, by SWS and by FWS, increased the occurrence o f the sleep state and o f the SWS phase, decreased the F W S occurrence, and reduced the mean duration o f the sleep state, the SWS and the F W S phases all significantly. Except for the FWS, the values following h i p p o c a m p e c t o m y were all significantly different f r o m corresponding values following cortical lesion. After cortical lesion, and m o r e prominently after hippocampectomy, the sleep sequence including only one SWS phase increased at the cost o f sequences with alternating SWS and F W S phases. Circadian variation o f sleep was preserved after hippocampectomy. H i p p o c a m p e c t o m y , but not cortical lesion, was followed by reduction in the occurrence, mean duration, and total time occupied by F W S more conspicuously in the daytime than at night. The h i p p o c a m p u s was inferred to be conducive to the maintenance o f sleep.

REFERENCES | ANDY, O. J., WEBSTER, C. L., MUKAWA,J., AND BONN, P., Electrophysiological comparisons of

the dorsal and ventral hippocampus. In P. PASSOUANT(Ed.), Physiologie de l'Hippocampe, Colloques Int. C.N.R.S., No. 107, C.N.R.S., Paris, 1962, pp. 411~-27. 2 CADILHAC, J., ET PASSOUANT-FONTAINE,TH., D6charges 6pileptiques et activit6 61ectrique de veille et de sommeil dans l'hippocampe au cours de l'ontog6n6se, In P. PASSOUANT(Ed.), Physiologie de l'Hippocampe, Colloques Int. C.N.R.S., No. 107, C.N.R.S., Paris, 1962, pp. 429-442. 3 CADILHAC,J., PASSOUANT=FONTAINE,TH.) ET PASSOUANT)P., Modifications de l'activit6 de l'hippocampe suivant les divers stades du sommeil spontan6 che z le chat, Rev. neurol., 105 ( 1961) 171-176. 4 CLEMENTE,C. O., AND STERMAN,M. O., Basal forebrain mechanisms for internal inhibition and sleep. In S. S. KETY, E. V. EVARTSAND H. L. WILLIAMS(Eds.), Sleep and Altered States of Consciousness, Williams and Wilkins, Baltimore, Md., 1967, pp. 127-147. 5 FAURE,J., Le sommeil 'paradoxal' du lapin dans ses aspects anatomo-fonctionnels et hormonaux. In M. JOUVET(Ed.), Aspects Anatomo-fonctionnels de la Physiologie du Sommeil, Colloques Int. C.N.R.S., No. 127, C.N.R.S., Paris, 1965, pp. 241-283. 6 FAURE, J., BENSCH,C., ET VINCENT)D., R61e d'un syst6me mesenc6phalolimbique dans la 'phase paradoxale' du sommeil chez le lapin, C.R. Soc. Biol. (Paris), 156 (1962) 70-74. 7 GRANT, L. D., AND JARRARD,L. E., Functional dissociation within hippocampus, Brain Research, 10 (1968) 392-401. 8 HERNANDEZ=PE6N,R., Central neuro-humoral transmission in sleep and wakefulness. In K. AKERT, C. BALLY, AND .L P. SCHADE(Eds.), Sleep Mechanisms, Progress in Brain Research, Vol. 18, Elsevier, Amsterdam, 1965, pp. 96-117. 9 HESS,W. R., Vegetative Funktionen und Zwischenhirn, Helv. physiol, pharmacol. Acta, Suppl. 4 (1947) 1-65. 10 JARRARD, L. E., Behavior of hippocampal lesioned rats in home cage and novel situations, Physiol. Behav., 3 (1968) 65-70. 11 JOUVET,M., MICHEL, F., ET COURJON, J., Sur un stade d'activit6 61ectrique c6r6brale rapide au cours du sommeil physiologique, C.R. Soc. Biol. (Paris), 153 (1959) 1024-1028. Brain Research, 29 (1971) 223-236

236

c. KIM el al.

12 KAADA, B. R., JANSEN,J., JR., AND ANDERSEN, P., Stimulation of the hippocampus and medial cortical areas in unanesthetized cats, Neurology (Minneap.), 3 (1953) 844-857. 13 KAADA,B. R., AND JASPER,H., Respiratory responses to stimulation of temporal pole, insula and hippocampal and limbic gyri in man, Arch. Neurol. Psychiat. (Chic.), 68 (1952) 609-619. 14 KHAZAN, N., AND SAWYER, C. H., Rebound recovery from deprivation of paradoxical sleep in the rabbit, Proc. Soc. exp. Biol. ( N. Y.), 114 (1963) 536-539. 15 KIM, C., CHOI, H., KIM, J. K., CHANG, H. K., PARK, R. S., AND KANG, 1. Y., General behavioral activity and its component patterns in hippocampectomized rats, Brain Research, 19 (1970) 379-394. 16 LENA, C., AND PARMEGGIANI,P. L., Hippocampal theta rhythm and activated sleep, Helv. physiol. pharmacol. Acta, 22 (1964) 120-135. 17 LISS~K, K., GRASTY~N,E., CSANAKY,A., KI~KESI,F., AND VEREaV, GY., A study of hippocampal function in the waking and sleeping animal with chronically implanted electrodes, Acta physiol. pharmacol, neerl., 6 (1957) 451-459. 18 MACLEAN,P. D., Chemical and electrical stimulation of hippocampus in unrestrained animals. II. Behavioral findings, Arch. Neurol. Psychiat. (Chic.}, 78 (1957) 128-142. 19 NAUTA, W. J. H., Hypothalamic regulation of sleep in rats. An experimental study, J. Neurophysiol., 9 (1946) 285-316. 20 PARMEGGIANI,P. L., Reizeffekte aus Hippocampus und Corpus mammillare der Katze, Heir. physiol, pharmaeol. Acta, 18 (1960) 523-536. 21 PARMEGGIANI,P. L., Sleep behavior elicited by electrical stimulation of cortical and subcortical structures in the cat, Helv. physiol, pharmacol. Acta, 20 (1962) 347-367. 22 PARMEGGIANI,P. L., On the functional significance of the hippocampal 0-rhythm. In W. R. ADEY AND T. TOKIZANE(Eds.), Structure and Function of the Limbic System, Progress in Brain Research, Vol. 27, Elsevier, Amsterdam, 1967, pp. 413-441. 23 PARMEGGIANI, P. L., UND SALVATORELLI, G., Archicorticale Regulierung der bioelektrischen T/itigkeit der prim/iren H6rrinde, Heir. physiol, pharmacol. Acta, 19 (1961) C94-C96. 24 PASSOUANT, P., ET CADILHAC, J., Les rythmes theta hippocampiques au cours du sommeil. In P. PASSOUANT (Ed.), Physiologie de l'Hippocampe, Colloques Int. C.N.R.S., No. I07, C.N.R.S.~ Paris, 1962, pp. 331-347. 25 RIMBAUD,L., PASSOUANT,P., ET CADILHAC, J., Participation de l'hippocampe h la r6gulation des 6tats de veille et de sommeil, Rev. neurol., 93 (1955) 303-308. 26 SEGUNDO, J. P., ARANA, R., MIGLIARO, E., VILLAR, J. E., GARCIA GUELFI, A., AND GARCIA AUSTT, E. H., Respiratory responses from fornix and wall of third ventricle in man, J. Neurophysiol., 18 (1955) 96-101. 27 STERMAN,M. B., KNAUSS,T., LEHMANN,O., AND CLEMENTE,C. D., Circadian sleep and waking patterns in the laboratory cat, Electroenceph. clin. Neurophysiol., 19 (1965) 509-517. 28 STUMPF,CH., The fast component in the electrical activity of rabbit's hippocampus, Electroenceph. clin. Neurophysiol., 18 (1965) 477486. 29 TORII, S., Two types of pattern of hippocampal electrical activity induced by stimulation of hypothalamus and surrounding parts of rabbit's brain, Jap. J. PhysioL, l l (1961) 147-157. 30 URSIN, R., Sleep stage relations within the sleep cycles of the cat, Brain Research, 20 (1970) 91-97. 31 VOTAW,C. L., Certain functional and anatomical relations of the cornu Ammonis of the macaque monkey. I. Functional relations, J. comp. Neurol., 112 (1959) 353-382. 32 WOOLSEY,C. N., Organization of cortical auditory system. In W. A. ROSENBLITH(Ed.), Sensory Communication, M.I.T. Press, Cambridge, Mass., 1961, pp. 235-257.

Brain Research, 29 (1971) 223-236