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Effects of brain-stem stimulation upon hippocampal electrical activity, somatomotor reflexes and autonomic functions
ELECTROENCEPHALOGRAPHYAND CLINICAL NEUROPHYSIOLOGY
375
EFFECTS OF B R A I N - S T E M S T I M U L A T I O N U P O N H I P P O C A M P A L ELECTRICAL ACTIVITY, S O M A T O M O T O R REFLEXES A N D A U T O N O M I C F U N C T I O N S TOSHIKATSU YOKOTA AND BUNICHI FUJIMORI
Department of Physiology, Hokkaido University School of Medicine, Sapporo (Japan) (Received for publication: November 2, 1962) (Resubmitted: April 1, 1963)
In recent years, it has been demonstrated that some structures of the limbic system and brainstem reticular formation are capable of modifying hippocampal electrical activity. Green and Arduini (1954) elicited synchronization of hippocampal electrical activity from a large subcortical area extending from the midbrain tegmentum forward through the hypothalamus to the preoptic and septal regions. On the other hand, Briicke et al. (1959) produced desynchronization of hippocampal regular slow waves by stimulation of the precomissural medial septum. Extensive studies of hippocampal electrical activity have been made by Tokizane et al. (1960), Torii and Kawamura (1960) and Torii (1961). This last author classified hippocampal electrical response to stimulation of the hypothalamus and surrounding parts of rabbit's brain into three types; slow wave, fast wave and intermediate responses. On the basis of his experiments, he stated that there are two functional systems within the brain which can influence the electrical activity of the hippocampus, viz., the slow wave-inducing system and the fast wave-inducing system. The functional significance of these changes in hippocampal electrical activity has not yet been fully clarified, although a certain parallelism between hippocampal electrical activity and blood pressure had been suggested by Torii and Kawamura (1960). In the present study, therefore, we have attempted to relate changes in hippocampal electrical activity with those of spinal motor reflexes and of autonomic functions. METHODS
Experiments were performed on 78 adult cats
immobilized with Flaxedil and under careful local anesthesia. In one series of experiments (43 cats) skin potential of foot pads, the monosynaptic gastrocnemius and the mono- as well as polysynaptic peroneal reflexes, were observed with special reference to associated changes in hippocampal activity. Under ether anesthesia, the trachea was cannulated and laminectomy as well as a partial craniotomy were performed. Wound margins were treated with procaine and also scalp, orbits and external auditory meati were locally anesthetized. The animal was mounted in a stereotaxic instrument (Todai Noken type). Flaxedil was then administered intravenously just beyond the point of respiratory paralysis, artificial respiration being maintained throughout the experiment. All spinal ventral roots below L~ were bilaterally severed. The monosynaptic gastrocnemius and the mono- as well as polysynaptic peroneal reflexes-were recorded from the ventral root of L6 or L7 on the right side by the use of the conventional method. Either gastrocnemius or the peroneal nerves were stimulated with single pulses of 0.1 msec duration at the rate of one every 3 sec. Skin potentials were recorded from pads of forepaw (see below). In the other series of experiments (35 cats), skin potentials of foot pads and blood pressure of bilaterally vagotomized animals were recorded simultaneously with hippocampal electrical activity. Skin potentials were recorded with a DC amplifier and an ink-writing oscillograph. The galvanic skin reflex (GSR) was elicited by stimulation of the proximal stump of the severed sciatic or peroneal nerve with a single pulse of 1 msec duration. Blood pressure was measured Electroenceph. clin. Neurophysiol., 1964, 16:375-382
376
T.
YOKOTA
AND
B. FUJIMORI
from one femoral artery with an electromanometer and recorded with an ink-writing oscillograph simultaneously with the skin potentials. Throughout these two series of experiments, the actual recording began more than 2 h after the cessation of ether inhalation. The electrical activity of the hippocampus was recorded on the right side and the brain stimulation was applied to the left side. The electrical activity of the hippocampus was occasionally analyzed with an
RESULTS
A. Hippocampal electrical response to stimulation o f the brain Changes of hippocampal electrical activity caused by stimulation of subcortical brain structures, were classified into the following four types: synchronization; desynchronization A; desynchronization B; and intermediate response. 1. Synchronization: Hippocampal slow waves
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"Synchronization" caused by stimulation of posteromedial hypothalamic region. With increase in strength of stimulation (A ~ D), hippocampal slow waves progressively increase in amplitude as well as in frequency. Period of brain stimulation is indicated by a horizontal bar.
electronic frequency analyser consisting of band pass filters and integrators (San'Ei Instr. Inc. Co.). For stimulation of subcortical brain structures, co-axial electrodes were used consisting of a steel tube of 0.5 m m in diameter containing a 100/z needle. Repetitive square pulses were delivered through these from a constant voltage stimulator. The duration of each pulse was 0.5 msec and the frequency was 50/sec. The accuracy of the electrode placements was routinely verified histologically. The effects of brain stimulation upon skin potentials were classified into three types; facilitatory, inhibitory and mixed. Criteria for such classification are described in detail elsewhere (Yokota and Fujimori 1963).
become regular and increase in both amplitude and frequency. This type of response corresponds to that described by Green and Arduini (1954) and could be elicited by stimulation of the medial preoptic area, the medial hypothalamic region and the dorsolateral part of the midbrain tegmentum. Fig. 1 presents an example of this phenomenon which becomes particularly evident with progressive increase in strength of stimulation. 2. Desynchronization A: Hippocampal slow waves are abolished and fast (15-30/sec) waves increase in amplitude. This type of response corresponds to the "fast wave response" of Torii (1961) and may be elicited by stimulation Electroenceph. clin. Neurophysiol.,
1964,
16:375-382
377
CORRELATIONS OF HIPPOCAMPAL ACTIVITY
Originol EEG
I sec JlOO,uv
A
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Fig. 2 "Desynchronization A" caused by stimulation of lateral preoptic area. A record of automatic frequency analysis. During brain stimulation, slow wave components (6e, 6~) decrease, whereas fast wave components (~,/3~, t32) increase. 6~: 1-2 c/see; 61: 2-4 c/see; 0: 4-8 c/see; 6: 8-13 c/see;/3a : 13-20 c/see;/32:20-30 clsec;/33:30-60 c/sec.
of the amygdala (nucleus amygdaloideus lateralis and area amygdaloidea anterior) and of the lateral preoptic area. Fig. 2 gives an example of the phenomenon which is clearly revealed by automatic frequency analysis. It was worth noting that during or following strong stimulation of these same areas hippocampal seizure discharges could occasionally be elicited. 3. Desynchronization B: Hippocampal slow waves are desynchronized but there is no increase in amplitude of fast waves. This type of response could be elicited by the stimulation of the bulbar ventromedial reticular formation. A typical record of this type is reproduced in Fig. 3 where the phenomenon can be seen with automatic frequency analysis. Stimulation of the area capable of producing this type of response did not elicit hippocampal seizure discharge as in the case of "desynchronization A". 4. "Intermediate response": Synchronization of slow waves is evoked with weak stimulation whereas desynchronization is elicited with stronger stimulation. This type of response could
be produced by stimulation of the posterolateral hypothalamic region and from the preoptic area, between the preoptic "synchronization" and "desynchronization A" area. A typical record of this phenomenon is reproduced in Fig. 4.
B. Changes in spinal motor reflexes and autonomic functions associated with different types of hippocampal electrical response Changes in spinal motor rel]exes and autonomic functions were investigated and related to each type of hippocampal response. 1. Synchronization: The monosynaptic gastrocnemius and the mono- as well as polysynaptic peroneal reflexes were diffusely facilitated in association with this type of hippocampal phenomenon (Fig. 5). A facilitatory response of skin potential was observed, concomitant with elevation of blood pressure. 2. Desynchronization A: In association with this hippocampal response, the gastrocnemius and peroneal reflexes were diffusely inhibited (Fig. 6). Blood pressure was depressed by weak, Electroenceph. clin. Neurophysiol., 1964, 16:375-382
378
T. YOKOTA AND B. FUJIMORI
original EEG
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Fig. 3 "Desynchronization B" caused by stimulation of bulbar ventromedial reticular formation. A record of automatic frequency analysis. During brain stimulation, slow wave components (63, 61) decrease, whereas fast wave components (ill, flz, f13) do not show appreciable change. (For explanations, see Fig. 2.)
B
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Fig. 4 "Intermediate response" caused by stimulation of posterolateral hypothalamus. With weak stimulation (A, B), slow waves are synchronized. With stronger stimulation (C, D), slow waves are desynchronized.
Electroenceph. clin. Neurophysiol., 1964, 16:375-382
379
CORRELATIONS OF H1PPOCAMPAL ACTIVITY
A Stim.
Gastro.
t
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B
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Peron. S t i m .
~
I mV 5 msec
Neocortex Hippocarnpus
~ Skin Pofenfiol
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;
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Fig. 5 Effects of stimulation of posteromedial hypothalamic region. Hippocampal slow waves are synchronized. Monosynaptic gastrocnemius and monosynaptic peroneal reflexes are facilitated: A and B before, and A' and B' during stimulation. Facilitatory response of skin potential appears. The arrows indicate sciatic nerve stimulation.
and increased by strong stimulation of the "desynchronization A" area. It was worth noting that in spite of such blood pressure elevation, hippocampal slow waves were markedly desynchronized and the amplitude of the fast waves increased considerably. The depression of blood pressure due to weak stimulation did not disappear after intravenous administration of atropine (0.3 mg/kg). As for skin potential of the foot pads, a facilitatory response was evoked with strong stimulation (Fig. 5), notwithstanding the above mentioned inhibition of somatomotor and vasomotor functions. 3. Desynehronization B: This type of hippocampal response was associated with diffuse inhibition of the gastrocnemius and peroneal reflexes, together with an inhibitory response of skin potential, while blood pressure was elevated. However, depression of blood pressure could be produced by the stimulation of the "desynchronization B" area after intravenous administration of Nembutal (10-20 mg/kg). De-
pression of blood pressure did not disappear through atropinization. 4. "Intermediate response": With the stimulation of the "intermediate response" area, facilitatory responses of the peroneal reflexes and of skin potential were obtained, while the gastrocnemius reflex was inhibited (Fig. 7). As for blood pressure, it would rise in the absence of anesthesia, whereas a depression was observed after intravenous administration of Nembutal (10-20 mg/kg). The above noted results are summarized in Table I. DISCUSSION
As far as the functional significance of hippocampal electrical activity is concerned, Green and Arduini (1954) stated that the appearance of regular slow waves is a specialized paleocortical arousal reaction. This finding was confirmed by other investigators (Liberson and Akert 1955; Gangloff and Monnier 1956; MacLean 1957). Electroenceph. clin. Neurophysiol., 1964, 16:375-382
T. YOKOTA AND B. FUJIMORI
380
A'
A Gastro. Stim.
i
B Peron. Stim.
B,
_yL,_
J I mV 5 msec
Neocortex i sec I IOO/~V
Hippocampus
Skin Potential ,
-
.
Fig. 6 Effects of s t i m u l a t i o n of a m y g d a l a (area a m y g d a l o i d e a anterior). H i p p o c a m p a l slow waves are desynchronized a n d fast waves are increased in amplitude. M o n o s y n a p t i c g a s t r o c n e m i u s a n d m o n o - as well as polysynaptic peroneal reflexes are inhibited. Skin potential is facilitated. (See Fig. 5 for additional explanations.) TABLE I Effects o f s t i m u l a t i o n o f each area u p o n h i p p o c a m p a l electrical activity, spinal m o t o r reflexes a n d a u t o n o m i c functions Response Area stimulated (cases)
Hippocampus . . . . Slow waves Fast waves
A m y g d a l a (14)
Desynchronization
Medial preoptic area (12)
Synchronization
Lateral preoptic area (12)
Desynchronization
Preoptic intermediate area (18)
•' I n t e r m e d i a t e "
Medial h y p o t h a l a m i c region (23)
Synchronization
Posterolateral h y p o t h a l a m i c region (18)
"Intermediate'"
Dorsolateral midbrain t e g m e n t u m (15) Bulbar ventromedial reticular formation (32)
Increase
Gastrocn. reflex
Peroneal reflexes
--
--
-
-
--
-
Blood pressure ............ W i t h o u t With anesthesia y
Skin potential
+
Increase A
A,
i
Y
Synchronization Desynchronization
N o increase
O n each cat, from one to f o u r sites were examined. In each case, h i p p o c a m p a l E E G and skin potential were always observed in association with either the g a s t r o c n e m i u s as well as peroneal reflexes or blood pressure. In the case o f blood pressure, results refer to unanesthetized cats a n d to cats under N e m b u t a l . In the cases o f spinal m o t o r reflexes and o f skin potential, ( ÷ ) is facilitation, while ( - - ) is inhibition.
Electroenceph. clhl. Neurophysiol., 1964, 16:375-3,?,2
381
CORRELATIONS OF HIPPOCAMPAL ACTIVITY
Gastro.
Stim.
A
Peron.
Sti m.
a
'
B'
-
-
-
B"
-
I
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!
/
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!
i
......
~
J
,.v
5 ~c
Neocortex HiDpocompus
Skin
,
Potential
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,
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Io t
Fig. 7 Effects of stimulation of posterolateral hypothalamic region. "Intermediate response" of hippocampal electrical activity is elicited. Monosynaptic gastrocnemius reflex is inhibited, while mono- as well as polysynaptic peroneal reflexes are facilitated: A and B are before, A' and B', during, and A" and B'" after stimulation.
Facilitatory response of skin potential is observed. On the other hand, Grasty/m et al. (1959) stated that desynchronization of hippocampal electrical activity is an expression of enhanced activity and that the rhythmic slow waves represent an inhibitory state. An attempt to relate hippocampal electrical activity with blood pressure was made by Torii and K a w a m u r a (1960), who stated that stimulation of the amygdaloid nucleus, the septal region and the preoptic area generally caused a fall in blood pressure concomitant with the appearance of fast waves in the hippocampal record, whereas stimulation of the posterior hypothalamus produced a rise in blood pressure concomitant with the presence of hippocampal regular slow waves. On the basis of their results, these authors suggested that the electrical activity of the hippocampus appears to be an indicator of autonomic function at least as far as blood pressure is concerned. In his latest report, furthermore, Torii (1961) stated that the fast wave-inducing system
passing through medial forebrain bundle is concerned with parasympathetic activity, whereas the slow wave-inducing system, including the longitudinal fascicles of SchLitz, is concerned with sympathetic activity. Therefore, he suggested that the development of rhythmic slow waves is an expression of enhanced activity of the sympathetic nervous system. In his classification of hippocampal electrical responses, Torii (1961) seems to assume that desynchronization of hippocampal slow waves is associated with increase of fast wave amplitude. In the present experiment, however, it was found that this is not always the case. Therefore, hippocampal electrical responses to the stimulation of the brain were classified into four types, and an attempt was made to investigate the functional significance of these two components: slow and fast waves. As a result, it was found that synchronization of hippocampal slow waves was associated with enhancement of somatomotor, sudoElectroenceph. clin. Neurophysiol., 1964, 16:375-382
382
T. YOKOTAAND B. FUJIMORI
motor and vasomotor activities. On the other hand, desynchronization of hippocampal slow waves was associated with inhibition of somatomotor activity together with inhibition of either vasomotor or sudomotor activity. It was also found that these areas, the stimulation of which would produce desynchronization, were capable of inhibiting vasomotor activity under appropriate conditions, viz., after Nembutal administration. On the basis of these results, the present study seems to suggest that the slow wave components of hippocampal electrical activity have indeed a close relationship with somatomotor and vasomotor activities. As for its fast wave components, however, it was impossible to relate them with either somatomotor and sudomotor or vasomotor functions. SUMMARY
In order to understand better the functional significance of hippocampal electrical activity, an attempt has been made to relate its changes with those of somatomotor, sudomotor and vasomotor activities. Experiments were conducted with locally anesthetized cats under Flaxedil. The animals were bilaterally vagotomized in the study of blood pressure. Four types of hippocampal electrical responses to the stimulation of various subcortical brain structures were observed. 1. "Synchronization" (produced by the stimulation of the medial preoptic area, the medial hypothalamic region and the dorsolateral part of the midbrain tegmentum) was associated with facilitation of the monosynaptic gastrocnemius and mono- as we!l as polysynaptic peroneal reflexes, elevation of blood pressure and facilitation of skin potentials. 2. "Desynchronization A " (elicited by the stimulation of the amygdala and the lateral preoptic area) was associated with inhibition of the gastrocnemius and peroneal reflexes, and depression of blood pressure. The skin potentials could be facilitated with strong stimulation. 3. "Desynchronization B" (elicited by the stimulation of the bulbar ventromedial reticular formation) was associated with inhibition of the gastrocnemius and peroneal reflexes, skin potentials and elevation of blood pressure. How-
ever, depression of the latter was obtained after Nembutal administration. 4. "Intermediate response" (elicited by the stimulation of the posterolateral hypothalamic region and the preoptic area) was associated with facilitation of the peroneal reflexes and of the skin potential, and with inhibition of the gastrocnemius reflex. Blood pressure, elevated in the absence of anesthesia, was depressed after Nembutal administration. In view of these experimental results, it is suggested that the slow wave components of hippocampal electrical activity might have a close relationship with somatomotor and vasomotor activities. The present study has been supported by grants from the Rockefeller Foundation and from the Japanese Ministry of Education. REFERENCES BR/3CKE, P., PETSCHE,H., PILLAT,B. und DEISENHAMMER,
E. Die Beeinflussung der Hippocampal-arousalReaktion beim Kaninchen durch elektrische Reizung im Septum. Pfliigers Arch. ges. Physiol., 1959, 269: 319-338. GANGLOEF, H. and MONNIER, M. Electrographic aspect
of "arousal" or attention reaction induced in the unanesthetized rabbit by the presence of a human being. Electroenceph. clin. Neurophysiol., 1956, 8: 623-629. GRASTY,~N, E., LISS~,K, K., MADARASZ, I, and DON-
HOFFER,H. Hippocampal electrical activity during the development of conditioned reflexes. Electroenceph. clin. Neurophysiol., 1959, 11 : 409-430. GREEN, J. D. and ARDUINI,A. A. Hippocampal electrical activity in arousal. J. Neurophysiol., 1954,17: 533-557. LmERSON, W. T. and AKERT, K. Hippocampal seizure state in guinea pig. Electroenceph. din. Neurophysiol., 1955, 7: 221-222. MACLEAN,P. P. Chemical and electrical stimulation of hippocampal unanesthetized animals. Arch. Neurol. Psychiat. (Chic.), 1957, 78: 113-142. TOKIZANE, T., KAWAMURA,H. and IMAMURA,G. Hypo-
thalamic activation upon electrical activities of paleoand archicortex. Neurol. medieochir., 1960, 2: 63-76. ToRn, S. Two types of pattern of hippocampal electrical activity induced by stimulation of hypothalamus and surrounding parts of rabbit's brain. Jap. J. Physiol., 1961, 11 : 147-157. TORn, S. and KAWAMORA,H. Effects of amygdaloid stimulation on blood pressure and electrical activity of hippocampus. Jap. J. Physiol., 1960, 10: 374-384. YOKOTA,T. and FUJIMORI,B. Inhibition of sympathetic activities by stimulation of limbic system. Jap. J. Physiol., 1963, 13: 137-143.
Reference: YOKOTA,T. and FUJIMORI,B. Effects of brain-stem stimulation upon hippocampal electrical activity,somatomotor reflexes and autonomic functions. Electroenceph. clin. Neurophysiol., 1964, 16: 375-382.
375
EFFECTS OF B R A I N - S T E M S T I M U L A T I O N U P O N H I P P O C A M P A L ELECTRICAL ACTIVITY, S O M A T O M O T O R REFLEXES A N D A U T O N O M I C F U N C T I O N S TOSHIKATSU YOKOTA AND BUNICHI FUJIMORI
Department of Physiology, Hokkaido University School of Medicine, Sapporo (Japan) (Received for publication: November 2, 1962) (Resubmitted: April 1, 1963)
In recent years, it has been demonstrated that some structures of the limbic system and brainstem reticular formation are capable of modifying hippocampal electrical activity. Green and Arduini (1954) elicited synchronization of hippocampal electrical activity from a large subcortical area extending from the midbrain tegmentum forward through the hypothalamus to the preoptic and septal regions. On the other hand, Briicke et al. (1959) produced desynchronization of hippocampal regular slow waves by stimulation of the precomissural medial septum. Extensive studies of hippocampal electrical activity have been made by Tokizane et al. (1960), Torii and Kawamura (1960) and Torii (1961). This last author classified hippocampal electrical response to stimulation of the hypothalamus and surrounding parts of rabbit's brain into three types; slow wave, fast wave and intermediate responses. On the basis of his experiments, he stated that there are two functional systems within the brain which can influence the electrical activity of the hippocampus, viz., the slow wave-inducing system and the fast wave-inducing system. The functional significance of these changes in hippocampal electrical activity has not yet been fully clarified, although a certain parallelism between hippocampal electrical activity and blood pressure had been suggested by Torii and Kawamura (1960). In the present study, therefore, we have attempted to relate changes in hippocampal electrical activity with those of spinal motor reflexes and of autonomic functions. METHODS
Experiments were performed on 78 adult cats
immobilized with Flaxedil and under careful local anesthesia. In one series of experiments (43 cats) skin potential of foot pads, the monosynaptic gastrocnemius and the mono- as well as polysynaptic peroneal reflexes, were observed with special reference to associated changes in hippocampal activity. Under ether anesthesia, the trachea was cannulated and laminectomy as well as a partial craniotomy were performed. Wound margins were treated with procaine and also scalp, orbits and external auditory meati were locally anesthetized. The animal was mounted in a stereotaxic instrument (Todai Noken type). Flaxedil was then administered intravenously just beyond the point of respiratory paralysis, artificial respiration being maintained throughout the experiment. All spinal ventral roots below L~ were bilaterally severed. The monosynaptic gastrocnemius and the mono- as well as polysynaptic peroneal reflexes-were recorded from the ventral root of L6 or L7 on the right side by the use of the conventional method. Either gastrocnemius or the peroneal nerves were stimulated with single pulses of 0.1 msec duration at the rate of one every 3 sec. Skin potentials were recorded from pads of forepaw (see below). In the other series of experiments (35 cats), skin potentials of foot pads and blood pressure of bilaterally vagotomized animals were recorded simultaneously with hippocampal electrical activity. Skin potentials were recorded with a DC amplifier and an ink-writing oscillograph. The galvanic skin reflex (GSR) was elicited by stimulation of the proximal stump of the severed sciatic or peroneal nerve with a single pulse of 1 msec duration. Blood pressure was measured Electroenceph. clin. Neurophysiol., 1964, 16:375-382
376
T.
YOKOTA
AND
B. FUJIMORI
from one femoral artery with an electromanometer and recorded with an ink-writing oscillograph simultaneously with the skin potentials. Throughout these two series of experiments, the actual recording began more than 2 h after the cessation of ether inhalation. The electrical activity of the hippocampus was recorded on the right side and the brain stimulation was applied to the left side. The electrical activity of the hippocampus was occasionally analyzed with an
RESULTS
A. Hippocampal electrical response to stimulation o f the brain Changes of hippocampal electrical activity caused by stimulation of subcortical brain structures, were classified into the following four types: synchronization; desynchronization A; desynchronization B; and intermediate response. 1. Synchronization: Hippocampal slow waves
IV
hfV
G
i~
,.'~.
J
!
2V .
i
'
7 ' .' 2,'
2.5V Fig.
'
J
.
,
' .
I sec I IO0=v 1
"Synchronization" caused by stimulation of posteromedial hypothalamic region. With increase in strength of stimulation (A ~ D), hippocampal slow waves progressively increase in amplitude as well as in frequency. Period of brain stimulation is indicated by a horizontal bar.
electronic frequency analyser consisting of band pass filters and integrators (San'Ei Instr. Inc. Co.). For stimulation of subcortical brain structures, co-axial electrodes were used consisting of a steel tube of 0.5 m m in diameter containing a 100/z needle. Repetitive square pulses were delivered through these from a constant voltage stimulator. The duration of each pulse was 0.5 msec and the frequency was 50/sec. The accuracy of the electrode placements was routinely verified histologically. The effects of brain stimulation upon skin potentials were classified into three types; facilitatory, inhibitory and mixed. Criteria for such classification are described in detail elsewhere (Yokota and Fujimori 1963).
become regular and increase in both amplitude and frequency. This type of response corresponds to that described by Green and Arduini (1954) and could be elicited by stimulation of the medial preoptic area, the medial hypothalamic region and the dorsolateral part of the midbrain tegmentum. Fig. 1 presents an example of this phenomenon which becomes particularly evident with progressive increase in strength of stimulation. 2. Desynchronization A: Hippocampal slow waves are abolished and fast (15-30/sec) waves increase in amplitude. This type of response corresponds to the "fast wave response" of Torii (1961) and may be elicited by stimulation Electroenceph. clin. Neurophysiol.,
1964,
16:375-382
377
CORRELATIONS OF HIPPOCAMPAL ACTIVITY
Originol EEG
I sec JlOO,uv
A
/3,
,-..,~"---~
,,.
/
uz
ul
.C# .
~.
'"
C'2..
#_"L'3 . . . . . . . .
~
.
.
.
.
Fig. 2 "Desynchronization A" caused by stimulation of lateral preoptic area. A record of automatic frequency analysis. During brain stimulation, slow wave components (6e, 6~) decrease, whereas fast wave components (~,/3~, t32) increase. 6~: 1-2 c/see; 61: 2-4 c/see; 0: 4-8 c/see; 6: 8-13 c/see;/3a : 13-20 c/see;/32:20-30 clsec;/33:30-60 c/sec.
of the amygdala (nucleus amygdaloideus lateralis and area amygdaloidea anterior) and of the lateral preoptic area. Fig. 2 gives an example of the phenomenon which is clearly revealed by automatic frequency analysis. It was worth noting that during or following strong stimulation of these same areas hippocampal seizure discharges could occasionally be elicited. 3. Desynchronization B: Hippocampal slow waves are desynchronized but there is no increase in amplitude of fast waves. This type of response could be elicited by the stimulation of the bulbar ventromedial reticular formation. A typical record of this type is reproduced in Fig. 3 where the phenomenon can be seen with automatic frequency analysis. Stimulation of the area capable of producing this type of response did not elicit hippocampal seizure discharge as in the case of "desynchronization A". 4. "Intermediate response": Synchronization of slow waves is evoked with weak stimulation whereas desynchronization is elicited with stronger stimulation. This type of response could
be produced by stimulation of the posterolateral hypothalamic region and from the preoptic area, between the preoptic "synchronization" and "desynchronization A" area. A typical record of this phenomenon is reproduced in Fig. 4.
B. Changes in spinal motor reflexes and autonomic functions associated with different types of hippocampal electrical response Changes in spinal motor rel]exes and autonomic functions were investigated and related to each type of hippocampal response. 1. Synchronization: The monosynaptic gastrocnemius and the mono- as well as polysynaptic peroneal reflexes were diffusely facilitated in association with this type of hippocampal phenomenon (Fig. 5). A facilitatory response of skin potential was observed, concomitant with elevation of blood pressure. 2. Desynchronization A: In association with this hippocampal response, the gastrocnemius and peroneal reflexes were diffusely inhibited (Fig. 6). Blood pressure was depressed by weak, Electroenceph. clin. Neurophysiol., 1964, 16:375-382
378
T. YOKOTA AND B. FUJIMORI
original EEG
I secJlOO,M
<, 0
o~
-
?iYl
~
T T -
.
.
.
.
.
.
--
.
.
.
.
.
.11
"
Fig. 3 "Desynchronization B" caused by stimulation of bulbar ventromedial reticular formation. A record of automatic frequency analysis. During brain stimulation, slow wave components (63, 61) decrease, whereas fast wave components (ill, flz, f13) do not show appreciable change. (For explanations, see Fig. 2.)
B
iv
1.5V
2V
'
2.SV
I s ~ IO0/~V
Fig. 4 "Intermediate response" caused by stimulation of posterolateral hypothalamus. With weak stimulation (A, B), slow waves are synchronized. With stronger stimulation (C, D), slow waves are desynchronized.
Electroenceph. clin. Neurophysiol., 1964, 16:375-382
379
CORRELATIONS OF H1PPOCAMPAL ACTIVITY
A Stim.
Gastro.
t
I
B
B,
Peron. S t i m .
~
I mV 5 msec
Neocortex Hippocarnpus
~ Skin Pofenfiol
_
;
,,~ ~'d~,~'~:i ~ ~ ,/:~L'~,~.,
~
t
~
,~!
i see I ~oo/,v .... -TT-/..~,.,
,o
..clSmv
t
t
Fig. 5 Effects of stimulation of posteromedial hypothalamic region. Hippocampal slow waves are synchronized. Monosynaptic gastrocnemius and monosynaptic peroneal reflexes are facilitated: A and B before, and A' and B' during stimulation. Facilitatory response of skin potential appears. The arrows indicate sciatic nerve stimulation.
and increased by strong stimulation of the "desynchronization A" area. It was worth noting that in spite of such blood pressure elevation, hippocampal slow waves were markedly desynchronized and the amplitude of the fast waves increased considerably. The depression of blood pressure due to weak stimulation did not disappear after intravenous administration of atropine (0.3 mg/kg). As for skin potential of the foot pads, a facilitatory response was evoked with strong stimulation (Fig. 5), notwithstanding the above mentioned inhibition of somatomotor and vasomotor functions. 3. Desynehronization B: This type of hippocampal response was associated with diffuse inhibition of the gastrocnemius and peroneal reflexes, together with an inhibitory response of skin potential, while blood pressure was elevated. However, depression of blood pressure could be produced by the stimulation of the "desynchronization B" area after intravenous administration of Nembutal (10-20 mg/kg). De-
pression of blood pressure did not disappear through atropinization. 4. "Intermediate response": With the stimulation of the "intermediate response" area, facilitatory responses of the peroneal reflexes and of skin potential were obtained, while the gastrocnemius reflex was inhibited (Fig. 7). As for blood pressure, it would rise in the absence of anesthesia, whereas a depression was observed after intravenous administration of Nembutal (10-20 mg/kg). The above noted results are summarized in Table I. DISCUSSION
As far as the functional significance of hippocampal electrical activity is concerned, Green and Arduini (1954) stated that the appearance of regular slow waves is a specialized paleocortical arousal reaction. This finding was confirmed by other investigators (Liberson and Akert 1955; Gangloff and Monnier 1956; MacLean 1957). Electroenceph. clin. Neurophysiol., 1964, 16:375-382
T. YOKOTA AND B. FUJIMORI
380
A'
A Gastro. Stim.
i
B Peron. Stim.
B,
_yL,_
J I mV 5 msec
Neocortex i sec I IOO/~V
Hippocampus
Skin Potential ,
-
.
Fig. 6 Effects of s t i m u l a t i o n of a m y g d a l a (area a m y g d a l o i d e a anterior). H i p p o c a m p a l slow waves are desynchronized a n d fast waves are increased in amplitude. M o n o s y n a p t i c g a s t r o c n e m i u s a n d m o n o - as well as polysynaptic peroneal reflexes are inhibited. Skin potential is facilitated. (See Fig. 5 for additional explanations.) TABLE I Effects o f s t i m u l a t i o n o f each area u p o n h i p p o c a m p a l electrical activity, spinal m o t o r reflexes a n d a u t o n o m i c functions Response Area stimulated (cases)
Hippocampus . . . . Slow waves Fast waves
A m y g d a l a (14)
Desynchronization
Medial preoptic area (12)
Synchronization
Lateral preoptic area (12)
Desynchronization
Preoptic intermediate area (18)
•' I n t e r m e d i a t e "
Medial h y p o t h a l a m i c region (23)
Synchronization
Posterolateral h y p o t h a l a m i c region (18)
"Intermediate'"
Dorsolateral midbrain t e g m e n t u m (15) Bulbar ventromedial reticular formation (32)
Increase
Gastrocn. reflex
Peroneal reflexes
--
--
-
-
--
-
Blood pressure ............ W i t h o u t With anesthesia y
Skin potential
+
Increase A
A,
i
Y
Synchronization Desynchronization
N o increase
O n each cat, from one to f o u r sites were examined. In each case, h i p p o c a m p a l E E G and skin potential were always observed in association with either the g a s t r o c n e m i u s as well as peroneal reflexes or blood pressure. In the case o f blood pressure, results refer to unanesthetized cats a n d to cats under N e m b u t a l . In the cases o f spinal m o t o r reflexes and o f skin potential, ( ÷ ) is facilitation, while ( - - ) is inhibition.
Electroenceph. clhl. Neurophysiol., 1964, 16:375-3,?,2
381
CORRELATIONS OF HIPPOCAMPAL ACTIVITY
Gastro.
Stim.
A
Peron.
Sti m.
a
'
B'
-
-
-
B"
-
I
lib
!
/
i
!
i
......
~
J
,.v
5 ~c
Neocortex HiDpocompus
Skin
,
Potential
~
,
__
t sec I IoopV
Io t
Fig. 7 Effects of stimulation of posterolateral hypothalamic region. "Intermediate response" of hippocampal electrical activity is elicited. Monosynaptic gastrocnemius reflex is inhibited, while mono- as well as polysynaptic peroneal reflexes are facilitated: A and B are before, A' and B', during, and A" and B'" after stimulation.
Facilitatory response of skin potential is observed. On the other hand, Grasty/m et al. (1959) stated that desynchronization of hippocampal electrical activity is an expression of enhanced activity and that the rhythmic slow waves represent an inhibitory state. An attempt to relate hippocampal electrical activity with blood pressure was made by Torii and K a w a m u r a (1960), who stated that stimulation of the amygdaloid nucleus, the septal region and the preoptic area generally caused a fall in blood pressure concomitant with the appearance of fast waves in the hippocampal record, whereas stimulation of the posterior hypothalamus produced a rise in blood pressure concomitant with the presence of hippocampal regular slow waves. On the basis of their results, these authors suggested that the electrical activity of the hippocampus appears to be an indicator of autonomic function at least as far as blood pressure is concerned. In his latest report, furthermore, Torii (1961) stated that the fast wave-inducing system
passing through medial forebrain bundle is concerned with parasympathetic activity, whereas the slow wave-inducing system, including the longitudinal fascicles of SchLitz, is concerned with sympathetic activity. Therefore, he suggested that the development of rhythmic slow waves is an expression of enhanced activity of the sympathetic nervous system. In his classification of hippocampal electrical responses, Torii (1961) seems to assume that desynchronization of hippocampal slow waves is associated with increase of fast wave amplitude. In the present experiment, however, it was found that this is not always the case. Therefore, hippocampal electrical responses to the stimulation of the brain were classified into four types, and an attempt was made to investigate the functional significance of these two components: slow and fast waves. As a result, it was found that synchronization of hippocampal slow waves was associated with enhancement of somatomotor, sudoElectroenceph. clin. Neurophysiol., 1964, 16:375-382
382
T. YOKOTAAND B. FUJIMORI
motor and vasomotor activities. On the other hand, desynchronization of hippocampal slow waves was associated with inhibition of somatomotor activity together with inhibition of either vasomotor or sudomotor activity. It was also found that these areas, the stimulation of which would produce desynchronization, were capable of inhibiting vasomotor activity under appropriate conditions, viz., after Nembutal administration. On the basis of these results, the present study seems to suggest that the slow wave components of hippocampal electrical activity have indeed a close relationship with somatomotor and vasomotor activities. As for its fast wave components, however, it was impossible to relate them with either somatomotor and sudomotor or vasomotor functions. SUMMARY
In order to understand better the functional significance of hippocampal electrical activity, an attempt has been made to relate its changes with those of somatomotor, sudomotor and vasomotor activities. Experiments were conducted with locally anesthetized cats under Flaxedil. The animals were bilaterally vagotomized in the study of blood pressure. Four types of hippocampal electrical responses to the stimulation of various subcortical brain structures were observed. 1. "Synchronization" (produced by the stimulation of the medial preoptic area, the medial hypothalamic region and the dorsolateral part of the midbrain tegmentum) was associated with facilitation of the monosynaptic gastrocnemius and mono- as we!l as polysynaptic peroneal reflexes, elevation of blood pressure and facilitation of skin potentials. 2. "Desynchronization A " (elicited by the stimulation of the amygdala and the lateral preoptic area) was associated with inhibition of the gastrocnemius and peroneal reflexes, and depression of blood pressure. The skin potentials could be facilitated with strong stimulation. 3. "Desynchronization B" (elicited by the stimulation of the bulbar ventromedial reticular formation) was associated with inhibition of the gastrocnemius and peroneal reflexes, skin potentials and elevation of blood pressure. How-
ever, depression of the latter was obtained after Nembutal administration. 4. "Intermediate response" (elicited by the stimulation of the posterolateral hypothalamic region and the preoptic area) was associated with facilitation of the peroneal reflexes and of the skin potential, and with inhibition of the gastrocnemius reflex. Blood pressure, elevated in the absence of anesthesia, was depressed after Nembutal administration. In view of these experimental results, it is suggested that the slow wave components of hippocampal electrical activity might have a close relationship with somatomotor and vasomotor activities. The present study has been supported by grants from the Rockefeller Foundation and from the Japanese Ministry of Education. REFERENCES BR/3CKE, P., PETSCHE,H., PILLAT,B. und DEISENHAMMER,
E. Die Beeinflussung der Hippocampal-arousalReaktion beim Kaninchen durch elektrische Reizung im Septum. Pfliigers Arch. ges. Physiol., 1959, 269: 319-338. GANGLOEF, H. and MONNIER, M. Electrographic aspect
of "arousal" or attention reaction induced in the unanesthetized rabbit by the presence of a human being. Electroenceph. clin. Neurophysiol., 1956, 8: 623-629. GRASTY,~N, E., LISS~,K, K., MADARASZ, I, and DON-
HOFFER,H. Hippocampal electrical activity during the development of conditioned reflexes. Electroenceph. clin. Neurophysiol., 1959, 11 : 409-430. GREEN, J. D. and ARDUINI,A. A. Hippocampal electrical activity in arousal. J. Neurophysiol., 1954,17: 533-557. LmERSON, W. T. and AKERT, K. Hippocampal seizure state in guinea pig. Electroenceph. din. Neurophysiol., 1955, 7: 221-222. MACLEAN,P. P. Chemical and electrical stimulation of hippocampal unanesthetized animals. Arch. Neurol. Psychiat. (Chic.), 1957, 78: 113-142. TOKIZANE, T., KAWAMURA,H. and IMAMURA,G. Hypo-
thalamic activation upon electrical activities of paleoand archicortex. Neurol. medieochir., 1960, 2: 63-76. ToRn, S. Two types of pattern of hippocampal electrical activity induced by stimulation of hypothalamus and surrounding parts of rabbit's brain. Jap. J. Physiol., 1961, 11 : 147-157. TORn, S. and KAWAMORA,H. Effects of amygdaloid stimulation on blood pressure and electrical activity of hippocampus. Jap. J. Physiol., 1960, 10: 374-384. YOKOTA,T. and FUJIMORI,B. Inhibition of sympathetic activities by stimulation of limbic system. Jap. J. Physiol., 1963, 13: 137-143.
Reference: YOKOTA,T. and FUJIMORI,B. Effects of brain-stem stimulation upon hippocampal electrical activity,somatomotor reflexes and autonomic functions. Electroenceph. clin. Neurophysiol., 1964, 16: 375-382.