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Characterization of the neurons in the region of solitary tract nucleus during sleep
Physiology & Behavior, Vol. 24, pp. 99-102. Pergamon Press and Brain Research Publ., 1980. Printed in the U.S.A.
Characterization of the Neurons in the Region of Solitary Tract Nucleus During Sleep KUNIHIRO
EGUCHI AND TOYOHIKO
SATOH
Department of Physiology, School of Dental Medicine, Aichi-Gakuin University, Nagoya, 464, Japan R e c e i v e d 10 M a y 1979 EGUCHI, K. AND T. SATOH. Characterization o f the neurons in the region of solitary tract nucleus during sleep.
PHYSIOL. BEHAV. 24(1) 99-102, 1980.--Single-unit recording was made from neurons in the region of solitary tract nucleus (NTS) of cats. Neurons discharging in correlation with cardiac or respiratory cycle were identified outside the NTS. They showed no obvious change in discharge rate during sleep-wakefulness cycle, and were unresponsive to electrical stimulation of the mesencephalic reticular formation (MRF), suggesting that they are not involved in slow wave sleep (SS) mechanism. More than half of the neurons recorded in the NTS showed an increase in discharge rate during, but not prior to, SS. Most of non-NTS neurons had during SS a discharge rate similar to that during wakefulness. The NTS neurons may be more related to SS mechanism than non-NTS neurons. The effectiveness of electrical stimulation of the MRF in driving or inhibiting the neurons of the NTS region was measured to be expressed by an index. Generally speaking, responses with greater S/W index ratio were excitatory, while those with smaller were inhibitory. During paradoxical sleep the effectiveness was usually reduced. Solitary tract nucleus Slow wave sleep Stimulation of mesencephalic reticular formation Cardiac cycle-related neuron Single-unit recording
S E V E R A L converging lines of evidence point to the importance of the neurons in or in the vicinity Of the solitary tract nucleus (NTS) for the manifestation of slow wave sleep (SS). The earliest evidence was induction of behavioral sleep following distention of the carotid sinus [7]. Later, it was shown that low frequency electrical stimulation delivered to the region of the NTS [9] or to the vago-aortic nerve [11] was able to produce E E G synchronization. However, it has been reported that neither bilateral vagotomy nor denervation of the carotid sinuses affects spontaneous E E G pattern [4]. Midpontine pretrigeminal transection, which brings about a long-lasting behavioral and E E G arousal, has indicated the presence of a powerful inhibitory system in the lower brainstem [ 1]. Perfusion of the NTS with serotonin produces E E G synchronization [6]. It has been suggested that the bulbar inhibitory system is operating by interacting with the midbrain reticular activating system [2]. Recently, reciprocal innervation between the midbrain reticular formation (MRF) and the NTS h a s been demonstrated by the evoked potential method [3]. Intracellular recording from the bulbar reticular formation has revealed several modes of signal transmission from the M R F [10]. It is generally accepted that states of sleep and wakefulness are the result of complex interaction of numerous structures which are mainly located in the lower brainstem. The mode of interaction of some of these structures has been studied electrophysiologically [5, 12, 13], resulting in the corroboration of the above concept. In the present experiment, single neurons in the region of the NTS were isolated with microelectrodes to investigate whether and how they are involved in SS mechanism. At-
tention was paid to their relationship with the cardiac cycle and to their response to electrical stimulation of the MRF. METHOD
Experiments were carded out on 6 adult cats weighing 2.8-3.8 Kg, which were operated under pentobarbital anesthesia (40 mg/Kg, IP). Electrodes for monitoring the EEG, ocular movements, and nuchal muscle tone were implanted chronically. A bipolar electrode made of stainless steel wire of 0.1 mm diameter and with a tip separation o f 1.0 mm was implanted stereotaxically to stimulate the M R F (A:3.0, R:3.5, V : - 0 . 5 ) . Occipital trepanation was performed to allow a unitary recording from the region of the NTS at the co-ordinates of P: 13-15 and LR: 1.5-3.0. After the animal has recovered from surgical wound, it was trained to sleep with a painless head restrainer. Recording microelectrodes were made of tungsten or elgiloy wire coated with solder glass. Glass micropipettes filled with 0.9% NaCI were also employed. The impedance of those electrodes was between 1 and 3 M ~ when measured at 1 KHz. Rectangular pulses of 0.1 msec duration were delivered every 2.5 sec to the MRF. Stimulus intensity was set at about 60% of the threshold of any visible motor response of the facial musculature. After the experiment, anodal current of 10/~A was given for 90 sec to the stimulated and recorded sites. The brain was fixed with 10% Formalin and serial sections of 20/~m thick were stained by Kliiver-Barrera method. Special attention was paid to the histological identification of the recording sites. The shrinkage of the brain tissue caused by the fixation procedures was measured on the basis of the distance between
C o p y r i g h t © 1980 B r a i n R e s e a r c h P u b l i c a t i o n s Inc.--0031-9384180/010099-04502.00/0
100
E G U C H I A N D SATOH
the reference points which had been marked stereotaxically. The positions of the tip of the recording electrodes were estimated by correcting the measures on the microstep driver with the above value. Computer analysis of individual units, which were stored on magnetic tapes with frequency response at 5 KHz, was performed to obtain the mean discharge rate, post-stimulus time histogram (PSTH), and cross-correlation with the QRS complex in the E K G during wakefulness (W), SS, and paradoxical sleep (PS). The magnitude of excitatory or inhibitory responses to the stimulation of the M R F was expressed by an index which was calculated by the following formula: I n d e x - R - BG D
and the mean number of spike specifically correlated with the cardiac cycle were not significantly altered at any phase of sleep-wakefulness cycle. Four of these neurons were, upon histological examination, located in the region dorsolateral to the NTS, and one was in the reticular formation ventral to the NTS (Fig. 1C). All of these neurons were unresponsive to electrical stimulation of the MRF. Additional 4 units, which could not be held for a long period, showed an excitatory response at about 100-300 msec after the QRS complex and were located outside the NTS. One unit showed a burst discharge synchronously with the early expiratory phase. This unit, which was located in the dorsal reticular formation contiguous to the NTS, was unresponsive to the M R F stimulation and did not show an alteration in the spontaneous discharge rate upon entering into SS. In more than half of the NTS neurons sampled (6 out of 11), transition from W to SS was associated with a significant increase in the spontaneous discharge rate (mean S/W= 1.73 _+ 0.31) (Table 1). However, the increase was neither evident prior to the occurrence of slow waves in the E E G nor most prominent at the initial part of SS. The increase seemed to proceed gradually and was most obvious during steady SS state. Almost all neurons (13 out of 14) sampled outside the NTS discharged during SS at a rate comparable to that during W. During PS, the spontaneous discharge rate was increased in many NTS and non-NTS neurons. However, there were also neurons with decreased or unaltered discharge rate. Electrical stimulation of the MRF gave rise to one to three deflections in the PSTH of 20 neurons (Fig. 1B). The responses seemed to be able to be divided in terms of latency into two groups: early (2-6 msec) and late (11-57 msec) responses. The duration was longer in late responses (14-84 msec), especially in inhibitory ones (19.5-84 msec). The responses which had, during SS, an index greater than that during W were mostly excitatory (9 out of 10) ( S / W > I . 3 in Fig. 2), while the responses with smaller index during SS
B'G'-- " -D-W-
where D, Dw, R, and BG stand for the duration of the evoked response in a given phase, that in W, the number of spikes during D, and the number of spikes assumed to be spontaneously occurring during D, respectively. Unequivocal deflections in the PSTH which were regarded as significant responses had an index greater than + 1.0 in the case of excitation and less than - 0 . 3 in the case of inhibition. When the above index and the spontaneous discharge rate of a single neuron were measured during the same two phases occurring at different time, their maximum variance was within 30%. Therefore, the difference greater than 30% was regarded as significant. The interpretation of the neuronal background responsible for the change in the index has already been discussed [13]. RESULTS A total of 27 neurons was recorded from the NTS region. Five units showed a burst discharge related with the cardiac rhythm. Three of them had an excitatory response at about 75-150 msec after the QRS complex in the EKG. The remaining two were inhibited during the systolic phase (Fig. 1A). In these 5 neurons both the spontaneous discharge rate
A
B
C
,o1 10
P15 - 200
0
400
msec
0
50
100
o
\
150 m'ec
mean Q R S i n t e r v a l
FIG. 1. (A) Temporal correlation of the discharge of a neuron inhibited during systolic period to the occurrence of 33 QRS complexes occurring at the abscissa "0". Neuronal discharge after the QRS complex was plotted to the right. Ordinate; impulse/33 measure cycles. (B) An example of the PSTH of an NTS neuron responding to MRF stimulation with initial strong excitation and subsequent weak inhibition. At the right, background discharge level. Ordinate; impulse/40 sweeps. (C) Localization of the neurons recorded. At the left, neurons correlated with cardiac (&) or respiratory (A) cycle. At the right, other neurons classified according to the background discharge rate SS/W; O: > 1.3, [:3: 1.3-0.7, @: <0.7. NTS: solitary tract nucleus, AP: area postrema, X: dorsal motor nucleus of vagus, XII: motor nucleus of XII nerve, IO: inferior olive, PT: pyramidal tract.
S O L I T A R Y TRACT N U C L E U S D U R I N G S L E E P
101
TABLE 1 BACKGROUND DISCHARGE RATE DURING SLEEP-WAKEFULNESS CYCLE
Site of recording
Ratio of the background discharge rate S/W P/S >1.3
1.3~0.7
<0.7
>1.3
1.3~0.7
<0.7
6
3
2
4
2
1
0
7
1
3
1
2
0 6
6 16 25
0 3
0 7
3 6 17
1 4
NTS Ventral to NTS Dorsolateral to NTS Subtotal Total
INDEX
RATIO
S/W ~>1.3
P/S
1.3- 0.7
000
<~ 0.7
>1.3
1.3-- 0.7
••
O000
INCREASED
UNALTERED
DECREASED
<~ 0.7 •011
[]DO• AA
O• [] •
00
OO
A
&AA
•
•
nun
000
nm •
O• []
A FIG. 2. Behavior of index in relation with the change in the background discharge rate and with the site of recording. BG: background discharge rate, ©: NTS, []: buibar reticular formation ventral to NTS, A: dorsolateral region to NTS, open symbols: excitatory response, filled symbols: inhibitory response.
were mostly inhibitory (9 out of 10) (S/W<0.7 in Fig. 2). There was no apparent selectivity in terms of latency or duration of the responses. During PS, the index was markedly decreased in almost all neurons when compared with both W and SS (P/S<0.7 in Fig. 2).
DISCUSSION
Consistent with previous reports [8,14], neurons which discharged in correlation with cardiac or respiratory cycle were identified outside the NTS. These neurons do not seem to be intimately related with sleep mechanism, because their discharge rate was not substantially influenced by sleepwakefulness cycle. All but one of other non-NTS neurons
had also an unaltered discharge rate upon transition from W to SS, though modulation often occurred during PS. In contrast, a considerable proportion of NTS neurons showed an increase in discharge rate during SS. Therefore, it might be that only those NTS neurons are, among the neurons sampied in this experiment, importantly involved in the elaboration of SS. However, it is not likely that those NTS neurons are playing a triggering role for the initiation of SS, because the increase in discharge rate did not occur until steady SS state is established. Effectiveness of the influence of the M R F upon the region of the NTS, as assessed from the behavior of the index, was modulated during SS in a somewhat characteristic manner; that is, enhancement of the influence was more often found in excitatory connections, while attenuation was pre-
102
EGUCHI AND SATOH
dominating in inhibitory connections. Such an alteration in the balance b e t w e e n excitatory and inhibitory connections might be important to the manifestation of SS. During PS, h o w e v e r , the index was strikingly reduced in a great majority of cases, j u s t as was found in the p o n t o m e s e n c e p h a l i c struc-
tures [13]. This seems to support further the idea that impairment of information transmission b e t w e e n different structures is one of the fundamental properties of the state of R E M sleep, possibly leading to the liberation of various p h e n o m e n a characterizing this state.
REFERENCES 1. Batini, C., G. Moruzzi, M. Palestini, G. F. Rossi and A. Zanchetti. Persistent patterns of wakefulness in the pretrigeminal mid-pontine preparation. Science 128: 30-32, 1958. 2. Bonvallet, M. and V. Bloch. Bulbar control of cortical arousal. Science 133: 1133-1134, 1961. 3. Bronzino, J. D. Evoked response study of postulated neural circuit associated with sleep-waking. Life Sci. 11: 419-433, 1972. 4. Cordeau, J. P. and M. Mancia. Evidence for the existence of an electroencephalographic synchronization mechanism originating in the lower brain stem. Electroenceph. clin. Neurophysiol. 11: 551-564, 1959. 5. Hobson, J. A., R. W. McCarley and P. W. Wyzinski. Sleep cycle oscillation: reciprocal discharge by two brainstem neuronal groups. Science 189: 55-58, 1975. 6. Key, B. J. and V. H. Mehta. Change in electrocortical activity induced by the perfusion of 5-hydroxytryptamine into the nucleus of the solitary tract. J. Neuropharmac. 16: 99-106, 1977. 7. Koch, E. Irradiation des pressorezeptorischen Kreislauf-reflexe auf das animale nervensystem. Z. Kreisl. Forsch. 24: 251-258, 1932.
8. Kreuter, F., D. W. Richter, H. Camerer and R. Senekowitsch. Morphological and electrical description of medullary respiratory neurons of the cat. Pfliigers Arch. 372: 7-16, 1977. 9. Magnes, J., G. Moruzzi and O. Pompeiano. Synchronization of the EEG produced by low frequency electrical stimulation of the region of the solitary tract. Archs ital. Biol. 99: 33-67, 1961. 10. Mancia, M., M. Mariotti and R. Spreafico. Caudo-rostral brain stem reciprocal influence in the cat. Brain Res. g0: 41-51, 1974. 11. Puizillout, J. J. and A. S. Foutz. Characteristics of the experimental reflex sleep induced by vago-aortic nerve stimulation. Electroenceph. clin. Neurophysiol. 42: 552-563, 1977. 12. Satoh, T. and N. Kanamori. Reticulo-reticular relationship during sleep and waking. Physiol. Behav. 15" 333-337, 1975. 13. Satoh, T., K. Egochi and K. Watabe. Functional relationship between cat brainstem neurons during sleep and wakefulness. Physiol. Behav. 22: 741-745, 1979. 14. Stroh-Werz, M., P. Langhorst and H. Camerer. Neuronal activity with cardiac rhythm in the nucleus of the solitary tract in cats and dogs. I. Different discharge patterns related to the cardiac cycle. Brain Res. 133: 65-80, 1977.
Characterization of the Neurons in the Region of Solitary Tract Nucleus During Sleep KUNIHIRO
EGUCHI AND TOYOHIKO
SATOH
Department of Physiology, School of Dental Medicine, Aichi-Gakuin University, Nagoya, 464, Japan R e c e i v e d 10 M a y 1979 EGUCHI, K. AND T. SATOH. Characterization o f the neurons in the region of solitary tract nucleus during sleep.
PHYSIOL. BEHAV. 24(1) 99-102, 1980.--Single-unit recording was made from neurons in the region of solitary tract nucleus (NTS) of cats. Neurons discharging in correlation with cardiac or respiratory cycle were identified outside the NTS. They showed no obvious change in discharge rate during sleep-wakefulness cycle, and were unresponsive to electrical stimulation of the mesencephalic reticular formation (MRF), suggesting that they are not involved in slow wave sleep (SS) mechanism. More than half of the neurons recorded in the NTS showed an increase in discharge rate during, but not prior to, SS. Most of non-NTS neurons had during SS a discharge rate similar to that during wakefulness. The NTS neurons may be more related to SS mechanism than non-NTS neurons. The effectiveness of electrical stimulation of the MRF in driving or inhibiting the neurons of the NTS region was measured to be expressed by an index. Generally speaking, responses with greater S/W index ratio were excitatory, while those with smaller were inhibitory. During paradoxical sleep the effectiveness was usually reduced. Solitary tract nucleus Slow wave sleep Stimulation of mesencephalic reticular formation Cardiac cycle-related neuron Single-unit recording
S E V E R A L converging lines of evidence point to the importance of the neurons in or in the vicinity Of the solitary tract nucleus (NTS) for the manifestation of slow wave sleep (SS). The earliest evidence was induction of behavioral sleep following distention of the carotid sinus [7]. Later, it was shown that low frequency electrical stimulation delivered to the region of the NTS [9] or to the vago-aortic nerve [11] was able to produce E E G synchronization. However, it has been reported that neither bilateral vagotomy nor denervation of the carotid sinuses affects spontaneous E E G pattern [4]. Midpontine pretrigeminal transection, which brings about a long-lasting behavioral and E E G arousal, has indicated the presence of a powerful inhibitory system in the lower brainstem [ 1]. Perfusion of the NTS with serotonin produces E E G synchronization [6]. It has been suggested that the bulbar inhibitory system is operating by interacting with the midbrain reticular activating system [2]. Recently, reciprocal innervation between the midbrain reticular formation (MRF) and the NTS h a s been demonstrated by the evoked potential method [3]. Intracellular recording from the bulbar reticular formation has revealed several modes of signal transmission from the M R F [10]. It is generally accepted that states of sleep and wakefulness are the result of complex interaction of numerous structures which are mainly located in the lower brainstem. The mode of interaction of some of these structures has been studied electrophysiologically [5, 12, 13], resulting in the corroboration of the above concept. In the present experiment, single neurons in the region of the NTS were isolated with microelectrodes to investigate whether and how they are involved in SS mechanism. At-
tention was paid to their relationship with the cardiac cycle and to their response to electrical stimulation of the MRF. METHOD
Experiments were carded out on 6 adult cats weighing 2.8-3.8 Kg, which were operated under pentobarbital anesthesia (40 mg/Kg, IP). Electrodes for monitoring the EEG, ocular movements, and nuchal muscle tone were implanted chronically. A bipolar electrode made of stainless steel wire of 0.1 mm diameter and with a tip separation o f 1.0 mm was implanted stereotaxically to stimulate the M R F (A:3.0, R:3.5, V : - 0 . 5 ) . Occipital trepanation was performed to allow a unitary recording from the region of the NTS at the co-ordinates of P: 13-15 and LR: 1.5-3.0. After the animal has recovered from surgical wound, it was trained to sleep with a painless head restrainer. Recording microelectrodes were made of tungsten or elgiloy wire coated with solder glass. Glass micropipettes filled with 0.9% NaCI were also employed. The impedance of those electrodes was between 1 and 3 M ~ when measured at 1 KHz. Rectangular pulses of 0.1 msec duration were delivered every 2.5 sec to the MRF. Stimulus intensity was set at about 60% of the threshold of any visible motor response of the facial musculature. After the experiment, anodal current of 10/~A was given for 90 sec to the stimulated and recorded sites. The brain was fixed with 10% Formalin and serial sections of 20/~m thick were stained by Kliiver-Barrera method. Special attention was paid to the histological identification of the recording sites. The shrinkage of the brain tissue caused by the fixation procedures was measured on the basis of the distance between
C o p y r i g h t © 1980 B r a i n R e s e a r c h P u b l i c a t i o n s Inc.--0031-9384180/010099-04502.00/0
100
E G U C H I A N D SATOH
the reference points which had been marked stereotaxically. The positions of the tip of the recording electrodes were estimated by correcting the measures on the microstep driver with the above value. Computer analysis of individual units, which were stored on magnetic tapes with frequency response at 5 KHz, was performed to obtain the mean discharge rate, post-stimulus time histogram (PSTH), and cross-correlation with the QRS complex in the E K G during wakefulness (W), SS, and paradoxical sleep (PS). The magnitude of excitatory or inhibitory responses to the stimulation of the M R F was expressed by an index which was calculated by the following formula: I n d e x - R - BG D
and the mean number of spike specifically correlated with the cardiac cycle were not significantly altered at any phase of sleep-wakefulness cycle. Four of these neurons were, upon histological examination, located in the region dorsolateral to the NTS, and one was in the reticular formation ventral to the NTS (Fig. 1C). All of these neurons were unresponsive to electrical stimulation of the MRF. Additional 4 units, which could not be held for a long period, showed an excitatory response at about 100-300 msec after the QRS complex and were located outside the NTS. One unit showed a burst discharge synchronously with the early expiratory phase. This unit, which was located in the dorsal reticular formation contiguous to the NTS, was unresponsive to the M R F stimulation and did not show an alteration in the spontaneous discharge rate upon entering into SS. In more than half of the NTS neurons sampled (6 out of 11), transition from W to SS was associated with a significant increase in the spontaneous discharge rate (mean S/W= 1.73 _+ 0.31) (Table 1). However, the increase was neither evident prior to the occurrence of slow waves in the E E G nor most prominent at the initial part of SS. The increase seemed to proceed gradually and was most obvious during steady SS state. Almost all neurons (13 out of 14) sampled outside the NTS discharged during SS at a rate comparable to that during W. During PS, the spontaneous discharge rate was increased in many NTS and non-NTS neurons. However, there were also neurons with decreased or unaltered discharge rate. Electrical stimulation of the MRF gave rise to one to three deflections in the PSTH of 20 neurons (Fig. 1B). The responses seemed to be able to be divided in terms of latency into two groups: early (2-6 msec) and late (11-57 msec) responses. The duration was longer in late responses (14-84 msec), especially in inhibitory ones (19.5-84 msec). The responses which had, during SS, an index greater than that during W were mostly excitatory (9 out of 10) ( S / W > I . 3 in Fig. 2), while the responses with smaller index during SS
B'G'-- " -D-W-
where D, Dw, R, and BG stand for the duration of the evoked response in a given phase, that in W, the number of spikes during D, and the number of spikes assumed to be spontaneously occurring during D, respectively. Unequivocal deflections in the PSTH which were regarded as significant responses had an index greater than + 1.0 in the case of excitation and less than - 0 . 3 in the case of inhibition. When the above index and the spontaneous discharge rate of a single neuron were measured during the same two phases occurring at different time, their maximum variance was within 30%. Therefore, the difference greater than 30% was regarded as significant. The interpretation of the neuronal background responsible for the change in the index has already been discussed [13]. RESULTS A total of 27 neurons was recorded from the NTS region. Five units showed a burst discharge related with the cardiac rhythm. Three of them had an excitatory response at about 75-150 msec after the QRS complex in the EKG. The remaining two were inhibited during the systolic phase (Fig. 1A). In these 5 neurons both the spontaneous discharge rate
A
B
C
,o1 10
P15 - 200
0
400
msec
0
50
100
o
\
150 m'ec
mean Q R S i n t e r v a l
FIG. 1. (A) Temporal correlation of the discharge of a neuron inhibited during systolic period to the occurrence of 33 QRS complexes occurring at the abscissa "0". Neuronal discharge after the QRS complex was plotted to the right. Ordinate; impulse/33 measure cycles. (B) An example of the PSTH of an NTS neuron responding to MRF stimulation with initial strong excitation and subsequent weak inhibition. At the right, background discharge level. Ordinate; impulse/40 sweeps. (C) Localization of the neurons recorded. At the left, neurons correlated with cardiac (&) or respiratory (A) cycle. At the right, other neurons classified according to the background discharge rate SS/W; O: > 1.3, [:3: 1.3-0.7, @: <0.7. NTS: solitary tract nucleus, AP: area postrema, X: dorsal motor nucleus of vagus, XII: motor nucleus of XII nerve, IO: inferior olive, PT: pyramidal tract.
S O L I T A R Y TRACT N U C L E U S D U R I N G S L E E P
101
TABLE 1 BACKGROUND DISCHARGE RATE DURING SLEEP-WAKEFULNESS CYCLE
Site of recording
Ratio of the background discharge rate S/W P/S >1.3
1.3~0.7
<0.7
>1.3
1.3~0.7
<0.7
6
3
2
4
2
1
0
7
1
3
1
2
0 6
6 16 25
0 3
0 7
3 6 17
1 4
NTS Ventral to NTS Dorsolateral to NTS Subtotal Total
INDEX
RATIO
S/W ~>1.3
P/S
1.3- 0.7
000
<~ 0.7
>1.3
1.3-- 0.7
••
O000
INCREASED
UNALTERED
DECREASED
<~ 0.7 •011
[]DO• AA
O• [] •
00
OO
A
&AA
•
•
nun
000
nm •
O• []
A FIG. 2. Behavior of index in relation with the change in the background discharge rate and with the site of recording. BG: background discharge rate, ©: NTS, []: buibar reticular formation ventral to NTS, A: dorsolateral region to NTS, open symbols: excitatory response, filled symbols: inhibitory response.
were mostly inhibitory (9 out of 10) (S/W<0.7 in Fig. 2). There was no apparent selectivity in terms of latency or duration of the responses. During PS, the index was markedly decreased in almost all neurons when compared with both W and SS (P/S<0.7 in Fig. 2).
DISCUSSION
Consistent with previous reports [8,14], neurons which discharged in correlation with cardiac or respiratory cycle were identified outside the NTS. These neurons do not seem to be intimately related with sleep mechanism, because their discharge rate was not substantially influenced by sleepwakefulness cycle. All but one of other non-NTS neurons
had also an unaltered discharge rate upon transition from W to SS, though modulation often occurred during PS. In contrast, a considerable proportion of NTS neurons showed an increase in discharge rate during SS. Therefore, it might be that only those NTS neurons are, among the neurons sampied in this experiment, importantly involved in the elaboration of SS. However, it is not likely that those NTS neurons are playing a triggering role for the initiation of SS, because the increase in discharge rate did not occur until steady SS state is established. Effectiveness of the influence of the M R F upon the region of the NTS, as assessed from the behavior of the index, was modulated during SS in a somewhat characteristic manner; that is, enhancement of the influence was more often found in excitatory connections, while attenuation was pre-
102
EGUCHI AND SATOH
dominating in inhibitory connections. Such an alteration in the balance b e t w e e n excitatory and inhibitory connections might be important to the manifestation of SS. During PS, h o w e v e r , the index was strikingly reduced in a great majority of cases, j u s t as was found in the p o n t o m e s e n c e p h a l i c struc-
tures [13]. This seems to support further the idea that impairment of information transmission b e t w e e n different structures is one of the fundamental properties of the state of R E M sleep, possibly leading to the liberation of various p h e n o m e n a characterizing this state.
REFERENCES 1. Batini, C., G. Moruzzi, M. Palestini, G. F. Rossi and A. Zanchetti. Persistent patterns of wakefulness in the pretrigeminal mid-pontine preparation. Science 128: 30-32, 1958. 2. Bonvallet, M. and V. Bloch. Bulbar control of cortical arousal. Science 133: 1133-1134, 1961. 3. Bronzino, J. D. Evoked response study of postulated neural circuit associated with sleep-waking. Life Sci. 11: 419-433, 1972. 4. Cordeau, J. P. and M. Mancia. Evidence for the existence of an electroencephalographic synchronization mechanism originating in the lower brain stem. Electroenceph. clin. Neurophysiol. 11: 551-564, 1959. 5. Hobson, J. A., R. W. McCarley and P. W. Wyzinski. Sleep cycle oscillation: reciprocal discharge by two brainstem neuronal groups. Science 189: 55-58, 1975. 6. Key, B. J. and V. H. Mehta. Change in electrocortical activity induced by the perfusion of 5-hydroxytryptamine into the nucleus of the solitary tract. J. Neuropharmac. 16: 99-106, 1977. 7. Koch, E. Irradiation des pressorezeptorischen Kreislauf-reflexe auf das animale nervensystem. Z. Kreisl. Forsch. 24: 251-258, 1932.
8. Kreuter, F., D. W. Richter, H. Camerer and R. Senekowitsch. Morphological and electrical description of medullary respiratory neurons of the cat. Pfliigers Arch. 372: 7-16, 1977. 9. Magnes, J., G. Moruzzi and O. Pompeiano. Synchronization of the EEG produced by low frequency electrical stimulation of the region of the solitary tract. Archs ital. Biol. 99: 33-67, 1961. 10. Mancia, M., M. Mariotti and R. Spreafico. Caudo-rostral brain stem reciprocal influence in the cat. Brain Res. g0: 41-51, 1974. 11. Puizillout, J. J. and A. S. Foutz. Characteristics of the experimental reflex sleep induced by vago-aortic nerve stimulation. Electroenceph. clin. Neurophysiol. 42: 552-563, 1977. 12. Satoh, T. and N. Kanamori. Reticulo-reticular relationship during sleep and waking. Physiol. Behav. 15" 333-337, 1975. 13. Satoh, T., K. Egochi and K. Watabe. Functional relationship between cat brainstem neurons during sleep and wakefulness. Physiol. Behav. 22: 741-745, 1979. 14. Stroh-Werz, M., P. Langhorst and H. Camerer. Neuronal activity with cardiac rhythm in the nucleus of the solitary tract in cats and dogs. I. Different discharge patterns related to the cardiac cycle. Brain Res. 133: 65-80, 1977.