Vol. 87, Issue 3, 1059-1065, September 1999
Pontine cholinergic mechanisms enhance trigeminally evoked
respiratory suppression in the anesthetized rat
Mathias
Dutschmann and
Horst
Herbert
Department of Animal Physiology, University of Tübingen,
Auf der Morgenstelle 28, D-72076 Tübingen, Germany
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ABSTRACT |
In the
present study, we investigated in anesthetized rats the influences of
the pontine rapid-eye-movement (REM) sleep center on trigeminally
induced respiratory responses. We evoked the nasotrigeminal reflex by
electrical stimulation of the ethmoidal nerve (EN5) and analyzed the
EN5-evoked respiratory suppression before and after injections into the
pontine reticular nuclei of the cholinergic agonist carbachol. After
injections of 80-100 nl of carbachol (20 mM), we observed a
decrease in respiratory rate, respiratory minute volume, and blood
pressure but an increase in tidal volume. In those cases in which
carbachol injections alone caused these REM sleep-like
autonomic responses, we also observed that the EN5-evoked respiratory
suppression was significantly potentiated. Unfortunately, carbachol
injections failed to depress genioglossus electromyogram (EMG)
effectively, because the EMG activity was already strongly depressed by
the anesthetic 
-chloralose. We assume that pontine carbachol
injections in our anesthetized rats cause autonomic effects that
largely resemble REM sleep-like respiratory and vascular responses. We
therefore conclude that the observed potentiation of EN5-evoked
respiratory suppression after carbachol might be due to REM
sleep-associated neuronal mechanisms. We speculate that activation of
sensory trigeminal afferents during REM sleep might contribute to
pathological REM sleep-associated respiratory failures.
sudden infant death syndrome; apnea; rapid-eye-movement sleep; Kölliker-Fuse; diving response
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INTRODUCTION |
THE NASOTRIGEMINAL REFLEX is a protective reflex of the
upper airways and is evoked by noxious stimulations of the nasal
mucosa. Profound autonomic responses are distinctive hallmarks of this reflex and include apnea, which protects the lower airways from invasion of noxious substances, as well as bradycardia and peripheral vasoconstriction that prevent a rapid progression of asphyxia (5, 17).
This reflex has been described for several species (1, 17, 19, 23, 24,
33) and plays a key role in initiation of the diving response, as
observed in marine mammals (5). The nasotrigeminal reflex is mediated
by the ethmoidal nerve (EN5), a branch of the ophthalmic division of
the sensory trigeminal nerve (28, 29). Recent studies (8-10) from
our laboratory revealed that the pontine Kölliker-Fuse nucleus
(KF) represents a mandatory relay for the EN5-evoked apnea and
bradycardia. The KF is part of the parabrachial complex (PB) and has
long been known as the pontine respiratory cell group that has a potent influence on the duration and termination of respiratory phases (7, 11,
21). The PB-KF complex has also been implicated in adapting respiration
to different behavioral states, especially to the sleep-wake cycle (27,
31). Lesions of the KF have resulted in pronounced REM sleep apneas (2,
3). Furthermore, during REM sleep-like states, the activity of neurons
in the PB-KF complex is decreased in correlation with respiratory
suppression (12, 13).
These data all suggest a crucial role for the KF in respiratory
adaptations during REM sleep. The ability of KF neurons to suppress
respiration in response to trigeminal stimulation and also during REM
sleep strengthens the idea that KF neurons might participate in
generating pathological phenomena, such as REM sleep apnea. This
assumption is in line with recent findings in diving mammals that show
pronounced nasotrigeminal reflex responses and also exhibit prominent
REM sleep apneas (4). Therefore, it is conceivable that the
nasotrigeminal reflex participates in the generation of REM sleep apnea.
REM sleep mechanisms have been extensively investigated by means of
microinjections of the cholinergic muscarinic-nicotinic agonist
carbachol into the pontine reticular nuclei, which induce REM sleep-like states in intact (14, 22) or acutely decerebrated (16,
32) animals. Recent studies reported that carbachol injections into the
medial pontine reticular nuclei of anesthetized animals induce postural
atonia (20, 34) and upper airway muscle hypotonia, accompanied by
respiratory suppression (15) that has been reported as typical for the
REM sleep-like state in awake or decerebrate animals (12, 16, 32).
These observations are supporting evidence that pontine cholinergic
mechanisms related to REM sleep and respiratory suppression can also be
investigated in anesthetized animals.
In the present study, we investigated the influence of pontine
cholinergic mechanisms on the expression of the nasotrigeminal reflex
responses in anesthetized rats. We analyzed the effect of carbachol
injection into the pontine reticular formation on arterial blood
pressure, heart rate, respiratory activity, and on genioglossus
electromyogram (EMG) to obtain criteria for a REM sleep-like state in
our anesthetized preparation. Most importantly, we stimulated the EN5
electrically and analyzed the EN5-evoked suppression of breathing
before and after carbachol injections into the pontine reticular
nuclei. We hypothesize that stimulation of sensory trigeminal afferents
might contribute to REM sleep apnea.
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METHODS |
The study was performed in accordance with the ethical guidelines for
the care and use of animals for experiments and was approved by the
local council for animal care (ZP1/95). Twenty male Wistar rats
(300-400 g) were anesthetized with a mixture of -chloralose
(150 mg/kg) and Urethane (60 mg/kg) injected intraperitoneally under
light ether preanesthesia. Anesthesia was maintained by intravenous
supplements of -chloralose, as indicated by responses to nociceptive
test stimuli. During the experimental sessions, the animals breathed
oxygen-enriched air and received saline infusions (0.5 ml/h iv) that
contained 10% glucose. The body temperature was maintained at 37°C
by a thermostatically controlled heating pad.
Surgical procedure.
The femoral artery was cannulated with polyethylene tubing to record
blood pressure and heart rate by using a Viggo-Spectramed transducer
and a Gould pressure processor. The femoral vein was cannulated for
drug and fluid injections. After a tracheotomy was performed, a
tracheal tube was inserted to record respiratory parameters via a Bell
and Howell pressure transducer. Thereafter, we isolated EN5, the
ethmoidal nerve that is a sensory branch of the trigeminal nerve that
innervates the nasal mucosa. The EN5 was identified as a ramification
of the ophthalmic nerve, which runs through the foramen ethmoidale on
the bottom of the orbital cavity. To provide electrical stimulation to
the nerve, the EN5 was placed on the exposed tips of Teflon-insulated
silver wires and then was covered with paraffin oil. Thereafter, the animal's head was fixed in a stereotaxic frame, and a craniotomy was
performed. In 10 animals, we recorded EMG activity from the genioglossus muscle. After the surgery, the animals were allowed to
stabilize for 1 h. Arterial blood pressure, heart rate, respiratory activity, and EMG activity were recorded, stored, and analyzed on a
MacLab/8s system. For details see Dutschmann and Herbert (10).
Experimental procedures.
At the beginning of each experiment, we evoked the nasotrigeminal
reflex by electrical stimulation of the EN5 with a train of pulses
(30-40 Hz, 100-µs pulse duration) for 10 s, with an intensity of
0.5-2 mA. This stimulus evoked the full expression of the
nasotrigeminal reflex, as described elsewhere (10), and served as the
control for an intact EN5. Thereafter, the stimulus intensities were
decreased to 20-200 µA, corresponding to a stimulation close to
threshold. This stimulus generally evoked only a slight respiratory
suppression, a slight rise in arterial blood pressure, and no
bradycardia response. For data collection, we exclusively used stimulations close to the threshold. For unilateral drug injections into the pontine reticular nuclei, we used glass
micropipettes with a tip diameter of 30-40 µm, filled with 20 mM
carbachol in saline (a mixed agonist for nicotinic and muscarinic
acetylcholine receptors). The pipettes were connected via tubing to a
multichannel picospritzer (General Valve). Pressure and opening times
were set to allow single puffs of 5-10 nl, as measured from the
miniscus level in the pipette. The injected volumes ranged between 80 and 100 nl. Immediately before each carbachol injection, one or two reference stimulations of the EN5, close to threshold, were performed. At 1-2 min after the last control stimulation, carbachol was
injected into the pontine reticular formation. After carbachol was
injected, EN5 stimulations were performed every 5 min at the beginning
of the experimental session and later every 10 min until recovery was
observed. At the end of each experiment, the rats received an overdose
of anesthetic (60 mg/kg Urethane) and were transcardially perfused with
saline, followed by 500 ml of 4% Formalin. Coronal sections through
the pons were cut at 50 µm on a freezing microtome, mounted on
slides, and stained with thionine. Sections through the pons were
analyzed with a light microscope to localize and reconstruct the
pipette track with the aid of a camera lucida. The track produced by
the pipettes as well as the lesions produced by the pressure injections
were generally clearly visible in our material. Furthermore, the
employed stereotaxic coordinates, together with an atlas of the rat
brain (25), were used to confirm the identified sites. Afterward, the
centers of the injection sites of each individual experiment were drawn
onto three representative sections through the pons (drawings modified
after Ref. 25).
Data analysis.
Carbachol injections into the pontine reticular nuclei generally led to
alterations in respiratory rate, tidal volume, blood pressure, and
heart rate. For statistical analysis, we compared the values (mean of 1 min of activity of the respective parameter) before carbachol injection
with values 10-15 min after carbachol injection and at recovery.
At 10-15 min after carbachol injections, we observed an
enhancement of the EN5-evoked respiratory depression. However, the cardiovascular responses to EN5 stimulation were generally inconsistent (both increases and decreases were observed) and, therefore, they were
not further analyzed. To quantify the effects of carbachol on the
EN5-evoked respiratory suppression, we calculated the total respiratory
volume (integrated signal of respiratory flow) during every individual
stimulation (10 s) before and after carbachol injections. These values
were then compared with the baseline values over 10 s before each
individual stimulation. The effects of the EN5 stimulations were
expressed as percent change of respiratory volume. The values of the
EN5 stimulations before the carbachol injections were then compared
with the values after carbachol injections and at recovery.
For statistical analysis, we used only those experiments in which the
carbachol injections were centered in the pontine reticular nuclei.
Furthermore, the carbachol injections alone had to induce "REM
sleep-specific" autonomic responses to be considered for analysis,
i.e., a decrease in blood pressure or a slight increase of <5%, a
decrease in respiratory rate and respiratory minute volume, and an
increase in tidal volume. For the analysis of numerical data (Table
1), we used ANOVA followed by
a Fisher least significant difference post hoc test. The tests were a
priori restricted to the differences between stimulations before and
after drug injection and the differences between stimulations after
drug injection and at recovery. Probability values at
P < 0.05 were considered to be
significant. All values were expressed as means ± SE.
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Table 1.
Summary of experiments in which carbachol injections centered in
pontine reticular nuclei induce autonomic responses specific to
rapid-eye-movement sleep
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RESULTS |
In the present study, we performed local injections of carbachol into
the pontine reticular nuclei of anesthetized rats to investigate the
influence of this cholinergic agonist on the strength of the EN5-evoked
respiratory suppression. We observed that EN5 stimulations near
threshold, performed 10-15 min after carbachol injections, showed
a significant potentiation of the EN5-evoked respiratory suppression
(Fig. 1). In contrast, the evoked cardiac and vascular responses to EN5 stimulations near the threshold were
fairly weak and inconsistent and thus were not further analyzed. Potentiation of the EN5-evoked respiratory suppression was observed only in those cases in which 1) the
carbachol injections were centered in the pontine reticular nuclei and
2) injections of the cholinergic
agonist alone led to specific changes of various autonomic parameters.
Unfortunately, pontine carbachol injections failed to induce
genioglossus hypotonia in the present study. This fact is due to the
influence of the anesthetic (-chloralose), which already suppresses
the genioglossus EMG profoundly (Fig. 2).
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Fig. 1.
Autonomic responses to 10-s electrical stimulation (stim.; solid bar)
of the ethmoidal nerve (EN5) before and after carbachol injections into
pontine reticular nuclei. A: recording
of arterial blood pressure (AP), heart rate (HR), and respiratory flow
(RF) in response to EN5 stimulation close to threshold (50 µA) before
carbachol injection; exp., expiration; insp., inspiration.
B: autonomic responses to carbachol
injection (arrow). C: autonomic
response to EN5 stimulation close to threshold 10 min after carbachol.
Note dramatic potentiation of EN5-evoked respiratory suppression and
EN5-evoked pressor response in this experiment.
D: respiratory response to EN5
stimulation 35 min after carbachol injection.
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Fig. 2.
Autonomic and electromyographic (EMG) responses to injection of 0.5 ml
-chloralose (15 mg iv). Note profound depression of genioglossus EMG
activity (bottom trace).
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The experiments that were statistically analyzed for their influence of
carbachol injections into the pontine REM sleep center are summarized
in Table 1. The injection sites were
clearly centered in the pontine reticular nuclei, particularly in the
PnO (Fig. 3). In all these experiments, we
observed, 10-15 min after carbachol injections, a highly
significant decrease in respiratory rate (P < 0.001), a significant increase
in tidal volume (P < 0.01), a
significant decrease in respiratory minute volume
(P < 0.01), and a tendency toward a
decrease in arterial blood pressure or, occasionally, a slight increase
(<5%). The heart rate did not change considerably after carbachol;
overall, a slight decrease was seen. In these experiments (Table 1), we
also found a highly significant potentiation of the EN5-evoked
respiratory suppression (P < 0.001).
Although, on average, EN5 stimulation close to threshold before
carbachol led to a respiratory suppression of 15.8%, the same stimulus
applied 10-15 min after carbachol caused a suppression of 55.1%.
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Fig. 3.
Semischematic line drawings of 3 representative sections through the
pontine reticular nuclei (A-C, from rostral to caudal)
demonstrate locations of unilateral carbachol-injection sites with
their individual experimental nos. in circles. Injection sites of
experiments 12 and 15 are not shown in these
drawings. Injection sites depicted in thick lines and bold nos.
represent experiments listed in Table 1. Injections shown in thin lines
are those listed in Table 2. Sections through pons are modified after
Paxinos and Watson (25), corresponding to plates 51, 53, 55 in that reference. A: IC, inferior colliculus; PAG,
periaqueductal gray; CnF, cuneiform nucleus; mlf, medial longitudinal
fasciculus; scp, superior cerebellar peduncle; PPTg, pedunculopontine
tegmental nucleus; DLL, dorsal nucleus of the lateral lemniscus; ILL,
intermediate nucleus of the lateral lemniscus; mcp, middle cerebellar
peduncle; rs, rubrospinal tract; RPO, rostral periolivary region; RtTg,
reticulotegmental nucleus of the pons; ml, medial lemniscus; py,
pyramidal tract; PnO, pontine reticular nucleus oralis. B:
PBL, lateral parabrachial nucleus; DTgP, dorsal tegmental nucleus,
pericentral part; DMTg, dorsomedial tegmental area; PnR, pontine raphe
nucleus; SOC, superior olivary complex; Mo5, motor trigeminal nucleus;
s5, sensory root of the trigeminal nerve; KF, Kölliker-Fuse
nucleus; Su5, supratrigeminal nucleus. C: PBM, medial
parabrachial nucleus; Pr5, principal sensory trigeminal nucleus; SubCA,
subcoeruleus, alpha; LDTg, laterodorsal tegmental nucleus; LC, locus
coeruleus; PnC, pontine reticular nucleus cuadalis.
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A significant recovery from the carbachol treatment was observed
50-70 min after drug injection for the respiratory rate
(P < 0.001) and the respiratory
minute volume (P < 0.05). Similarly, the carbachol-induced potentiation of the EN5-evoked respiratory suppression also showed a highly significant recovery
(P < 0.001). The tidal volume showed
only a tendency to recover, whereas blood pressure and heart rate had
increased compared with controls.
In Table 2, those experiments are grouped
in which the carbachol injections were not centered in the pontine
reticular nucleus oralis (PnO) proper (Fig. 3) and in which the
autonomic changes to drug injections did not fulfill the criteria of
REM sleep-specific autonomic responses, as defined in the
METHODS section. In general, these
experiments showed only a weak potentiation of the EN5-evoked respiratory suppression. In only two cases listed
(experiments 9 and
16), did we find a clear
potentiation of the EN5 response. However, in these experiments, we
found a rise in arterial blood pressure of >5%, and they were
therefore excluded from further statistical analysis.
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Table 2.
Summary of experiments in which carbachol injections were centered
outside the pontine reticular formation or did not induce autonomic
response specific to rapid-eye-movement sleep
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Verification of carbachol-injection sites in the pontine reticular
formation revealed a topography with respect to the degree of
potentiation of the EN5-evoked respiratory suppression (Fig. 3). In
those cases in which the injection sites were centered in the PnO (Fig.
3B), we observed a powerful
potentiation of the EN5-induced suppression of breathing. Effects were
considerably weaker after drug injections into the nucleus pontis
caudalis (PnC; Fig. 3C) or into
nuclei surrounding the PnO or PnC (e.g., experiments
5 and 18; Fig. 3,
B and
C).
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DISCUSSION |
Technical considerations.
Our results demonstrate that injections of carbachol into the pontine
reticular nuclei of anesthetized rats induced a profound change in
respiratory activity, such that respiratory rate and respiratory minute
volume were significantly decreased, whereas the tidal volume was
increased. Apparently, the increase in tidal volume could not
compensate for the decrease in respiratory rate and, consequently, the
respiratory minute volume was significantly reduced. Our observation
that pontine carbachol injections cause suppression of respiratory
activity is in general agreement with previous studies on REM
sleep-like states not only in awake (12, 13, 22) and decerebrate
animals (16, 32) but also in anesthetized rats (15). These studies
provide supporting evidence for our working hypothesis that, in our
anesthetized preparation, pontine carbachol injections also induce a
REM sleep-like respiratory suppression. Further evidence for the
induction of a REM sleep-like state by pontine carbachol injection is
provided by the arterial blood pressure response, which was generally
decreased or slightly increased in some experiments. According to
Shiromani et al. (30) a REM sleep-like state is indeed accompanied by a
decrease or a slight increase in arterial blood pressure in late REM
sleep states evoked by carbachol injections in awake animals.
However, we were not able to demonstrate in our deeply anesthetized
preparation a REM sleep-associated hypotonia of the genioglossus muscle. We observed that the genioglossus activity was already strongly
suppressed by the anesthetic alone; therefore, a further suppression by
carbachol could not unequivocally be seen. In contrast, others did
report postural atonia after pontine carbachol injection in animals
anesthetized with -chloralose (20, 34). This discrepancy might be
caused by differences in the depth of anesthesia employed in the
different studies. Consequently, on the basis of genioglossus activity,
we could not define a REM sleep-like state, as is possible in awake
animals. Furthermore, it has been reported that pontine carbachol
injections do not necessarily induce REM sleep-like states,
particularly in rats (6, 32). Our "effective" injection sites in
the PnO are generally in good agreement with a previous report (6),
whereas others show effective sites more dorsally in the pontine
reticular formation (16, 32).
The carbachol-induced respiratory and vascular effects observed in our
study are reminiscent of autonomic patterns observed after carbachol
induced REM sleep-like states in awake animals. We take this fact as
supporting evidence that we most likely also induced REM
sleep-associated neuronal mechanisms in our anesthetized rats. Thus it
is conceivable that the carbachol-induced potentiation of EN5-evoked
respiratory depression is correlated with REM sleep.
Potential mechanisms of enhanced EN5-evoked respiratory depression
after carbachol injection into the pontine REM sleep center.
The major finding of the present study concerns the effect of pontine
carbachol injections on the EN5-evoked respiratory suppression. Before
drug injections, EN5 stimulations, with stimulus currents close to
threshold, resulted only in a slight suppression of breathing. Shortly
after application of carbachol, the same stimulus induced a marked
suppression of breathing, even, in some cases, leading to an apnea. Our
observation is in line with a study in human infants (26), who
responded with brief apneas to nasotrigeminal air-puff stimulations
during natural REM sleep. The underlying central
mechanisms that mediate the potentiation of the EN5-evoked respiratory
suppression are not yet known. However, a potential candidate involved
in these processes is the PB-KF complex, because it has been shown that
pontine carbachol injections in fact alter the activity of PB-KF
neurons (12, 13, 22). A carbachol-induced decrease in PB-KF activity
could result in a decrease in respiratory rate, considering that the
PB-KF is part of the pneumotaxic center and thus is strongly involved
in the control of respiratory rate and phase transition (7).
Furthermore, the KF has been identified as a mandatory relay for the
EN5-evoked apnea (8-10) and thus represents the crucial
sensory-autonomic interface that transmits sensory trigeminal inputs to
the medullary respiratory network. Both respiratory-suppressive
mechanisms (the pontine carbachol and the nasotrigeminal suppression of
breathing) are apparently integrated in the KF. It is, therefore,
conceivable that the parallel occurrence and interaction in the KF of
both mechanisms may lead to the observed potentiation of the
nasotrigeminally induced respiratory suppression. The assumption that
the KF might be of importance for mediating REM sleep-related
respiratory depression is supported by anatomic evidence that shows
direct projections from the pontine REM sleep center to the PB-KF
complex (18). Nevertheless, projections from the pontine REM sleep
center to the ventral and dorsal respiratory group in the medullary
brain stem have also been documented (18).
In conclusion, we hypothesize that the respiratory rhythm is severely
vulnerable during REM sleep or REM sleep-like states. Activation of
sensory trigeminal afferents during REM sleep could easily trigger
centrally mediated apneas, which might contribute to pathological,
life-threatening phenomena, such as REM sleep apnea or sudden infant
death syndrome.
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ACKNOWLEDGEMENTS |
We thank Helga Zillus for technical assistance, Dr. Jo Ostwald for
valuable suggestions during the course of the study, and Dr. Michael
Koch for suggestions on the manuscript.
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FOOTNOTES |
This study was supported by the Deutsche Forschungsgemeinschaft
(He1842/6-1) and by the Graduiertenkolleg Neurobiologie,
Tübingen.
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: H. Herbert,
Universität Tübingen, Tierphysiologie, Auf der Morgenstelle
28, D-72076 Tübingen, Germany (E-mail:
horst.herbert{at}uni-tuebingen.de).
Received 2 March 1998; accepted in final form 5 May 1999.
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REFERENCES |
1.
Angell-James, J. E.,
and
M. de Burgh Daly.
Reflex respiratory and cardiovascular effects of stimulation of receptors of the nose of the dog.
J. Physiol. (Lond.)
220:
673-696,
1972[Abstract/Free Full Text].
2.
Baker, T. L.,
A. Netick,
and
W. C. Dement.
Sleep-related apneic and apneustic breathing following pneumotaxic lesion and vagotomy.
Respir. Physiol.
46:
271-294,
1981[Medline].
3.
Caille, D.,
J.-F. Vibert,
and
A. Hugelin.
Apneusis and apnea after parabrachial or Kölliker-Fuse nucleus lesion; influence of wakefulness.
Respir. Physiol.
45:
79-95,
1981[Medline].
4.
Castellini, M. A.
Dreaming about diving: sleep apnea in seals.
News Physiol. Sci.
11:
208214,
1996.
5.
De Burgh Daly, M.
Breath-hold diving: mechanisms of cardiovascular adjustments in the mammal.
Recent Adv. Physiol.
10:
201-245,
1984.
6.
Deurveilher, S.,
B. Hars,
and
E. Hennevin.
Pontine microinjection of carbachol does not reliably enhance paradoxical sleep in rats.
Sleep
20:
593-607,
1997[Medline].
7.
Dick, T. E.,
M. C. Bellingham,
and
D. W. Richter.
Pontine respiratory neurons in anesthetized cats.
Brain Res.
636:
259-269,
1994[Medline].
8.
Dutschmann, M.,
and
H. Herbert.
Fos expression in the rat parabrachial and Kölliker-Fuse nuclei after electrical stimulation of the trigeminal ethmoidal nerve and water stimulation of the nasal mucosa.
Exp. Brain Res.
117:
97-110,
1997[Medline].
9.
Dutschmann, M.,
and
H. Herbert.
The Kölliker-Fuse nucleus mediates the trigeminally induced apnea in the rat.
Neuroreport
7:
1432-1436,
1996[Medline].
10.
Dutschmann, M.,
and
H. Herbert.
NMDA and GABAA receptors in the rat Kölliker-Fuse area control cardio-respiratory responses evoked by trigeminal ethmoidal nerve stimulation.
J. Physiol. (Lond.)
510:
793-804,
1998[Abstract/Free Full Text].
11.
Fung, M.-L.,
W. Wang,
and
W. M. St. John.
Involvement of pontile NMDA receptors in inspiratory termination in rat.
Respir. Physiol.
96:
177-188,
1994[Medline].
12.
Gilbert, K. A.,
and
R. Lydic.
Muscarinic cholinoceptive reticular mechanisms and parabrachial neuron discharge: a novel experimental approach.
Neuroreport
4:
271-274,
1993[Medline].
13.
Gilbert, K. A.,
and
R. Lydic.
Parabrachial neuron discharge in the cat is altered during the carbachol-induced REM sleep-like state (DCarb).
Neurosci. Lett.
120:
241-244,
1990[Medline].
14.
Hobson, J. A.,
R. Lydic,
and
H. Baghdoyan.
Evolving concepts of sleep cycle generation from brain centers to neuronal populations.
Behav. Brain Sci.
9:
371-448,
1986.
15.
Horner, R. L.,
and
L. Kubin.
Rapid eye movement sleep (REMs)-like electrographic and respiratory changes following pontine carbachol in urethane anesthetized rats.
Soc. Neurosci. Abstr.
23:
794,
1997.
16.
Kimura, H.,
L. Kubin,
R. O. Davies,
and
A. I. Park.
Cholinergic stimulation of the pons depresses respiration in decerebrate cats.
J. Appl. Physiol.
69:
2280-2289,
1990[Abstract/Free Full Text].
17.
Kratschmer, F.
Über Reflexe von der Nasenschleimhaut auf Athmung und Kreislauf.
Sitzungsber. Math.-Nat. Classe Akad. Wissensch.
XVI:
147-170,
1870.
18.
Lawrence, H. L.,
B. Diane,
and
R. Lydic.
Respiratory nuclei share synaptic connectivity with pontine reticular regions regulating REM sleep.
Am. J. Physiol.
268 (Lung Cell. Mol. Physiol. 12):
L251-L262,
1995[Abstract/Free Full Text].
19.
Lin, Y. C.
Autonomic nervous control of cardiovascular response during diving in the rat.
Am. J. Physiol.
227:
601-605,
1974.
20.
López-Rodríguez, F.,
K. A. Kohlmeier,
J. Yamuy,
F. R. Morales,
and
M. H. Chase.
Muscle atonia can be induced by carbachol injections into the nucleus pontis oralis in cats anesthetized with -chloralose.
Brain Res.
699:
201-207,
1995[Medline].
21.
Lumsden, T.
Observations on the respiratory centres in the cat.
J. Physiol. (Lond.)
57:
153-160,
1923.
22.
Lydic, R.,
and
H. A. Baghdoyan.
Cholinergic pontine mechanisms causing state-dependent respiratory depression.
News Physiol. Sci.
7:
220-224,
1992.[Abstract/Free Full Text]
23.
Panneton, W. M.
Controlled bradycardia induced by nasal stimulation in the muskrat, Ondatra zibethicus.
J. Auton. Nerv. Syst.
30:
253-264,
1990[Medline].
24.
Panneton, W. M.,
and
P. Yavari.
A medullary dorsal horn relay for the cardiorespiratory responses evoked by stimulation of the nasal mucosa in the muskrat, Ondatra zibethicus.
Neuroscience
58:
605-625,
1995.
25.
Paxinos, G.,
and
C. Watson.
The Rat Brain in Stereotaxic Coordinates. San Diego, CA: Academic, 1997.
26.
Ramet, J.,
J.-P. Praud,
A.-M. D'Allest,
M. Dehan,
and
C. Gaultier.
Trigeminal airstream stimulation. Maturation-related cardiac and respiratory responses during REM sleep in human infants.
Chest
98:
92-96,
1990[Abstract/Free Full Text].
27.
Saito, H.,
K. Sakai,
and
M. Jouvet.
Discharge patterns of the nucleus parabrachialis lateralis neurons of the cat during sleep and waking.
Brain Res.
134:
59-72,
1977[Medline].
28.
Sant'Ambrogio, G.,
H. Tsubone,
and
F. B. Sant'Ambrogio.
Sensory information from the upper airway: role in the control of breathing.
Respir. Physiol.
102:
1-16,
1995[Medline].
29.
Sekizawa, S.,
and
H. Tsubone.
Nasal receptors responding to noxious chemical irritants.
Respir. Physiol.
96:
37-48,
1994[Medline].
30.
Shiromani, P. J.,
J. M. Siegel,
K. S. Tomaszewski,
and
D. J. McGinty.
Alterations in blood pressure and REM sleep after pontine carbachol microinfusion.
Exp. Neurol.
91:
285-292,
1986[Medline].
31.
Sieck, G. C.,
and
R. M. Harper.
Pneumotaxic area neuronal discharge during sleep-waking states in the cat.
Exp. Neurol.
67:
79-102,
1980[Medline].
32.
Taguchi, O.,
L. Kubin,
and
A. I. Pack.
Evocation of postural atonia and respiratory suppression by pontine carbachol in the decerebrate rat.
Brain Res.
595:
107-115,
1992[Medline].
33.
Tchobroutsky, C.,
C. Merlet,
and
P. Rey.
The diving reflex in rabbit, sheep and newborn lamb and its afferent pathways.
Respir. Physiol.
8:
108-117,
1969[Medline].
34.
Xi, M.-C.,
R.-H. Lui,
J. Yamuy,
F. R. Morales,
and
M. H. Chase.
Electrophysiological properties of lumbar motoneurones in the -chloralose anesthetized cat during carbachol-induced motor inhibition.
J. Neurophysiol.
78:
129-136,
1997[Abstract/Free Full Text].
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