www.elsevier.com / locate / bres
Research report
Laryngeal effects of stimulation of rostral and ventral pons in the
anaesthetized rat
a ,
*
a a a b´
J.P. Lara
, M.S. Dawid-Milner , M.V. Lopez , C. Montes , K.M. Spyer ,
a´
´
S. Gonzalez-Baron
a
´ ´
Department of Physiology, School of Medicine, University of Malaga, 29080 Malaga, Spain
b
Department of Physiology, Autonomic Neuroscience Institute, Royal Free and University College Medical School, University College, London, UK
Accepted 29 January 2002
Abstract
In order to study the importance of two pontine regions modulating laryngeal resistance, electrical current or microinjections of glutamate (10–30 nl, 1–3 nmol) were made into the pontine parabrachial complex and the A5 region in spontaneously breathing anaesthetized rats. Two distinct patterns of laryngeal and respiratory responses were elicited. An increase of subglottal pressure was accompanied with an expiratory facilitatory response consisted of a decrease in both respiratory rate and phrenic nerve activity. A decrease of subglottal pressure was accompanied with an inspiratory facilitatory response consisted of an increase in both respiratory rate and phrenic nerve activity. The modification of laryngeal calibre occurred during both respiratory phases in most cases. The concomitant cardiovascular changes of these responses were also analyzed. Controls using guanethidine to block autonomic responses which might interact with respiratory control were also made. Histological analysis of stimulation sites showed a topographical organization of these
¨
responses: laryngeal constriction was evoked from Kolliker–Fuse, medial parabrachial nuclei and A5 region, whilst the laryngeal dilation was evoked from the lateral parabrachial nucleus. 2002 Published by Elsevier Science B.V.
Theme: Endocrine and autonomic regulation
Topic: Respiratory regulation
Keywords: Respiratory and laryngeal regulation; Pons; Parabrachial; A5 region; Glutamate; Rat
1. Introduction strated previously in the rat that specific activation of cell bodies located in distinct regions of the parabrachial It is known that some pontine regions play a significant complex elicit two distinct respiratory responses: inspirat-role in modifying the basic respiratory rhythm generated ory (following lateral parabrachial activation) and expirat-by neurones located in the medulla oblongata. This pontine ory facilitatory responses (following medial parabrachial
¨
control of the ventilatory activity involves multiple aspects and Kolliker–Fuse activation) [8,26,33]. However, the that may be served by different neuronal groups respiratory role of the parabrachial complex, particularly
¨
[6,8,15,25,29,36]; it affects mainly the regulation of respi- the Kolliker–Fuse nucleus, is still unclear: using very ratory phases but also modulates airway tone and the small chemical stimuli, three types of respiratory responses activation of respiratory reflex responses [15,31,32,37]. have been described suggesting a complex organization of The respiratory role of the pons has largely been this nucleus participating in both inspiratory and expiratory considered to reflect the function of the parabrachial mechanisms [5,7].
complex. Its role has been investigated in different species In addition to the parabrachial complex, there are other [5,7,6,8,11,15,25,26,28,33,36]. We and others have demon- groups of pontine neurones that participate in respiratory regulation [5,7,8,11,15,22,36]. This laboratory has also shown that activation of neurones located in the ventral *Corresponding author. Tel.: 134-95-213-4212; fax: 1
34-95-213-catecholaminergic A5 pontine region, produces
cardiores-1650.
E-mail address: [email protected] (J.P. Lara). piratory responses [7,8], and we have suggestive evidence
0006-8993 / 02 / $ – see front matter 2002 Published by Elsevier Science B.V. P I I : S 0 0 0 6 - 8 9 9 3 ( 0 2 ) 0 2 3 6 4 - 8
for interactions between these neurons and those of the subglottic pressure with the ‘in situ’ isolated larynx parabrachial complex [9]. Important effects of respiratory technique [18,19,35] (Fig. 1), by passing a stream of inhibition are also elicited by trigeminal injections of humidified warm air through the proximal tracheal cannula glutamate, suggesting that apnea was elicited from the area and the larynx at a constant rate (1 ml / s). The inflow
¨
just ventral to the Kolliker–Fuse, rather than within it [7]. pressure (subglottic pressure) was measured as an index of The intertrigeminal region, a population of neurones laryngeal resistance. A catheter was introduced into the among the trigeminal motor rootless has been described as esophagus for the indirect measurement of pleural pres-an area capable of driving apneic responses [5]. These sure. The femoral artery and vein were cannulated for the respiratory responses following pontine activation were measurement of arterial pressure and the administration of accompanied by cardiovascular changes, indicating an drugs, respectively. The animals breathed spontaneously a integration of central cardiorespiratory control [6,8,26]. mixture of O2 enriched room air. End-tidal CO2 was The larynx constitutes the entrance to the lower airways. monitored (3–5%). Rectal temperature was maintained at It can be considered as a respiratory organ since glottal 37–388C using a servo-controlled heating pad.
movements related to the respiratory rhythm are present. The animals were positioned in a stereotaxic frame with They consist of glottal dilatation during inspiration and the upper incisor bar 3.3 mm below interaural line [38], glottal narrowing during early expiration [18]. These and fixed by clamps on the spinous processes of C7 and changes in the caliber of the glottis can modify respiratory L2. The phrenic nerve was isolated and placed on a bipolar function since they affect greatly airway resistance [19,21]. silver electrode for recording central respiratory drive We now suggest that the parabrachial complex and the A5 (bandpass 10 Hz to 10 kHz).
region may be important in regulating laryngeal calibre Multibarrel electrodes (tip size: 30–40 mm) were and, therefore, upper airway resistance. Accordingly, positioned stereotaxically in the parabrachial and the
¨
studying these effects may have clinical importance since Kolliker–Fuse nuclei (from 0.28 to21.04 mm, rostrocaud-it could add new information concerning the laryngeal role al to interaural line, 1.4–2.7 mm lateral to midline, from in apneas and its relation with pontine activation [13,27]. 3.8 to 1 mm deep to interaural line) and in the A5 region (from interaural line to 21.6 mm caudal, 2–3 mm lateral to midline, from 1 to 20.5 mm deep to interaural line). The barrels were filled with NaCl 1 M, glutamate 100 mM,
2. Material and methods saline 0.9% and Pontamine Sky Blue 10 mM. Laryngeal and cardiorespiratory changes were analyzed during elec-Experiments were performed on 16 spontaneously trical stimulation (10–40mA, 0.4-ms pulses, 50 Hz for 5 s) breathing Sprague–Dawley rats (body weight: 250–300 g), and glutamate injections (10–30 nl, 1–3 nmol, pH anaesthetized with sodium pentobarbitone (60 mg / kg i.p., 7.460.1, 5 s). Control saline injections were made. The initial dose, supplemented 2 mg / kg, i.v., as necessary). site of stimulation was marked with either an electrical The level of anesthesia was assessed by observing the lesion (250mA DC for 20 s) or injection of Pontamine Sky presence, or absence, of a significant withdrawal reflex to Blue (10–30 nl). Brains were perfused via the left ven-pinching a paw and the absence of alterations in blood tricule with formalin–saline, serially sectioned (100 mm)
pressure and heart rate. and counter-stained with neutral red.
Two independent cannulae were inserted into the trach- In six animals, pontine stimulation was made before, ea. Airflow was measured from a Fleisch pneumo- and after, the administration of guanethidine (10 mg / kg, tachograph attached to the distal tracheal cannula, and i.v) to examine whether the laryngeal and respiratory responses were due to reflex changes induced by the accompanying cardiovascular response.
Airflow, subglottal pressure, pleural pressure, phrenic nerve activity and arterial blood pressure were monitored and stored on digital tape for off-line analysis (Neuro-Corder DR-890; Global Lab DT2821G). These variables were recorded for 3 min starting 30 s before the beginning of the stimulation.
Measurements were made of subglottal pressure (peak expiratory values), inspiratory time (duration of the phrenic burst), expiratory time (period between phrenic burst), peak phrenic activity (100 ms constant integration), in-stantaneous respiratory frequency, mean blood arterial pressure and instantaneous heart rate.
Fig. 1. In situ isolated glottis technique. Schematic diagram showing the
Only data from animals in which the histology revealed
model of the ‘in situ’ isolated larynx technique (see explanation in the
complex or the A5 region were evaluated statistically. All 3. Results
data are presented as mean6S.D. For statistical
proce-dures, once the normality of the data was verified (Kol- Two distinct patterns of laryngeal and respiratory re-mogorov–Smirnoff coefficient), a paired sample test was sponses were elicited by glutamate injection and electrical applied to compare the control with the stimulation period stimulation of pontine structures: expiratory and inspirat-for each animal. Significance was taken at a probability of ory facilitatory responses (EFR and IFR, respectively).
P,0.05. The EFR consisted of a decrease in both respiratory rate
Fig. 2. Histological localization of the stimulation sites. Semi-schematic line drawings of coronal sections through the parabrachial complex and the A5 region from rostral (top left) to caudal (bottom right), showing the sites where stimuli were applied. Sites at which both electrical and glutamate injection caused a expiratory facilitatory response with an increase of subglottic pressure (n); sites at which glutamate failed to evoke that response although electrical stimulation was effective (s). Sites at which both electrical and glutamate injection caused an inspiratory facilitatory response with a decrease of subglottic pressure (j); sites at which glutamate failed to evoke that response although electrical stimulation was effective (h).
and phrenic nerve activity, accompanied by an increase of failed to evoke these responses although electrical stimula-subglottal pressure. The IFR consisted of an increase in tion had been effective on these sites.
both respiratory rate and phrenic nerve activity
accom-panied by a decrease of subglottal pressure. The change of 3.1. Laryngeal and respiratory responses evoked from
¨
laryngeal calibre occurred during both inspiratory and Kolliker –Fuse and medial parabrachial nuclei
expiratory phases in most cases. Both inspiratory and stimulations
expiratory subglottal pressure values increased during the
EFR; both inspiratory and expiratory subglottal pressure Electrical or glutamate stimuli increased subglottal values decreased during the IFR. In this paper, peak pressure (from 2.1560.48 to 4.7260.9 cmH O, P2 ,0.05 expiratory subglottal pressure values are cited throughout. and from 2.1060.53 to 4.5160.74 cmH O, P2 ,0.05, Cardiovascular changes were also elicited at these sites respectively) and decreased respiratory rate (from
(see later). 79.4611.4 to 53.4610.9 breaths / min, P,0.001 and from
On subsequent histological analysis of stimulation sites, 79.1611.7 to 46.5624.5 breaths / min, P,0.01, respective-it was clear that these two response patterns were elicrespective-ited ly) (Fig. 3). The changes in respiratory rate were due to a from distinct pontine regions (see Fig. 2): the glottal significant increase in expiratory time (from 0.53160.1 to
¨
constriction was evoked from Kolliker–Fuse, medial 0.87660.21 s, P,0.05 and from 0.54860.11 to parabrachial nuclei and A5 region stimulations, while 1.61661.14 s, P,0.01, respectively). Inspiratory time was glottal dilation was elicited from the lateral parabrachial unaffected. After termination of electrical stimulation, nucleus. Electrical stimulation was always effective in phrenic nerve activity returned to control levels within 10 eliciting these responses. On three occasions, glutamate s. The respiratory response to an injection of glutamate had
Fig. 3. Laryngeal and respiratory responses to electrical stimulation in the medial parabrachial nucleus. Phrenic nerve discharge, respiratory airflow, pleural pressure, subglottic pressure and integrated phrenic nerve discharge, showing a expiratory facilitatory response with increase of subglottic pressure during electrical stimulation (20mA, 0.4-ms pulses, 50 Hz for 5 s) in the medial parabrachial nucleus.
a mean duration of 4568 s. Occasionally stimuli produced 0.36160.12 s, P,0.05). After termination of electrical an apnoea lasting as long as 5 s. Saline injections at those stimulation phrenic nerve activity returned to control levels points elicited no changes in respiratory activity or within 10 s. The respiratory response to glutamate
in-laryngeal resistance. jection had a mean duration of 4568 s. Saline injections at
those points elicited no changes in any of these variables. 3.2. Laryngeal and respiratory responses evoked from
lateral parabrachial nucleus stimulations 3.3. Laryngeal and respiratory responses evoked from
A5 pontine region stimulations Electrical or glutamate stimulation decreased subglottal
pressure (from 2.4860.38 to 1.2360.25 cmH O, P2 ,0.05 Electrical or glutamate stimulation increased subglottal and from 2.4660.37 to 1.3260.24 cmH O, P2 ,0.05, pressure (from 2.0560.63 to 4.2260.54 cmH O, P2 ,0.05 respectively) and increased respiratory rate (from and from 2.0660.63 to 4.1660.81 cmH O, P2 ,0.05, 80.666.8 to 97.268.2 breaths / min, P,0.01 and from respectively) and decreased respiratory rate (from 77.867.4 to 101612.3 breaths / min, P,0.05, respectively) 85.9613.7 to 53.9617.8 breaths / min, P,0.001 and from (Fig. 4). The changes in respiratory rate were due to a 86.1614.1 to 55.18621.3 breaths / min, P,0.01, respec-significant decrease in expiratory time (from 0.48860.1 to tively) (Fig. 5). The changes in respiratory rate were due 0.26760.15 s, P,0.01 and from 0.47960.1 to 0.23360.14 to a significant increase of expiratory time (from s, P,0.01, respectively). Glutamate evoked also a signifi- 0.46960.17 to 1.31360.52 s, P,0.01 and from cant increase of inspiratory time (from 0.29260.1 to 0.45560.14 to 1.83560.62 0 s, P,0.01, respectively).
Fig. 4. Laryngeal and respiratory responses to electrical stimulation in the lateral parabrachial nucleus. Phrenic nerve discharge, respiratory airflow, pleural pressure, subglottic pressure and integrated phrenic nerve discharge, showing an inspiratory facilitatory response with decrease of subglottic pressure during electrical stimulation (10mA, 0.4-ms pulses, 50 Hz for 5 s) in the lateral parabrachial nucleus.
Fig. 5. Laryngeal and respiratory responses to glutamate microinjection in the A5 region. Phrenic nerve discharge, respiratory airflow, pleural pressure, subglottic pressure and integrated phrenic nerve discharge, showing a expiratory facilitatory response with increase of subglottic pressure during a glutamate injection (10 nl over 5 s) in the A5 region. The arrows shows the onset of injection.
There were no significant changes of inspiratory time. P,0.05, respectively). On three occasions, the pressor After termination of electrical stimulation phrenic nerve response elicited from A5 with glutamate was followed by activity returned to control levels within 10 s. The respira- a depressor response.
tory response to glutamate injection had a mean duration Heart rate increased during both electrical and glutamate ¨
of 4568 s. On occasions, either stimulus produced apnoea stimulation into medial parabrachial and Kolliker–Fuse lasting as long as 5 s. Saline injections at those points nuclei (from 378635 to 390637 beats / min, P,0.05 and
elicited no changes in these variables. from 377633 to 387637 beats / min, P,0.05), lateral
parabrachial nucleus (from 405632 to 414638 beats / min, 3.4. Cardiovascular responses to pontine stimulations P,0.05 and from 407635 to 417637 beats / min, P,0.05) and A5 region (from 414646 to 421651 beats / min, P,
A cardiovascular response was also elicited at all 0.05 and from 398648 to 405649 beats / min, P,0.05). locations (both within the parabrachial complex and A5 In six animals, either PB or A5 stimulation (three cases, region) where laryngeal and respiratory responses had been each) was made before and after guanethidine
administra-observed (Figs. 6 and 7). tion (10 mg / kg, i.v.). Guanethidine abolished the rise in
Blood pressure increased during both electrical and blood pressure and heart rate but had no effect on either glutamate stimulation in medial parabrachial nucleus and the laryngeal or the respiratory responses.
¨
Kolliker–Fuse nucleus (from 10866 to 146615 mmHg,
P,0.01 and from10766 to 144626 mmHg, P,0.001,
respectively), lateral parabrachial nucleus (from 10265 to 4. Discussion
138613 mmHg, P,0.01 and from 10667 to 135628
mmHg, P,0.01, respectively). Such stimulation in the A5 This study provides data concerning the laryngeal region elicited similar changes (from 10269 to 137615 effects elicited by two pontine regions, the parabrachial mmHg, P,0.01 and from 10169 to 115617 mmHg, complex and the A5 region, that participate in
cardiores-Fig. 6. Laryngeal and cardiorespiratory responses to electrical stimulation in the medial parabrachial nucleus. Integrated phrenic nerve discharge, subglottic pressure, blood pressure and instantaneous heart rate, showing an expiratory facilitatory response with increase of subglottic pressure, blood pressure and heart rate during electrical stimulation (20mA, 0.4-ms pulses, 50 Hz for 5 s) in the medial parabrachial nucleus.
piratory regulation. The changes in laryngeal resistance have found no references to equivalent data in the litera-were always accompanied by respiratory changes, the ture. We have included for statistical analysis only data pattern of which have been detailed in earlier studies from animals in which stable recordings were observed
[9,25]. before, during and after pontine stimulation.
An increase of subglottal pressure together with a In the present study, we used electrodes which permitted decrease in both respiratory rate and phrenic nerve activity both electrical stimulation and injection of glutamate at the (EFR) was evoked by stimulation of the medial parabrachi- same location. Electrical stimulation was used primarily to
¨
al and Kolliker–Fuse nuclei and also the A5 region. locate both the parabrachial complex and the A5 region. Conversely, a decrease of subglottal pressure together with The magnitude of the changes in subglottal pressure and an increase in both respiratory rate and phrenic nerve respiratory rate were similar using both methods of stimu-activity (IFR) was evoked by stimulation of the lateral lation. While the effects of electrical stimulation are very parabrachial nucleus. These results indicate that pontine difficult to interpret, the effects of glutamate microinjec-regions participate in a topographically organized control tion suggest that the elicited laryngeal and respiratory of the larynx. Both inspiratory and expiratory subglottal responses can be attributed to activation of cell bodies pressure values increased during the EFR; on few occa- located in these pontine regions and are not due to the sions the subglottal pressure stayed constant at the expirat- activation of axons of passage. In addition, the sites in ory value. Similarly, both inspiratory and expiratory which on three occasions glutamate injection failed to subglottal pressure values decreased during the IFR; on evoked responses although electrical stimulation was effi-few occasions the subglottal pressure remained constant at cient, indicate the stimulation of fibers of passage.
the inspiratory value, during expiration. The PB complex participates in central control of both
The isolated glottis technique has been used to study somatic and visceral functions. Sensory information via laryngeal responses before [19,21,37]. This technique has both the nucleus of the solitary tract [20] and spinal some advantages: it separates the lower airways from the afferents [4,14] converge on parabrachial neurones. We larynx, facilitates the study of modifications in neuro- have shown that activation of parabrachial neurones eli-muscular tone and abolishes the influence of variations of cited a laryngeal and cardiorespiratory pattern that could the airflow activating laryngeal reflexes. However, there be present in many responses as, for instance, cardiores-are difficulties recording subglottal pressure in the rat; we piratory reflexes or emotional behaviour. Especially, it is
Fig. 7. Laryngeal and cardiorespiratory responses to electrical stimulation in the lateral parabrachial nucleus. Integrated phrenic nerve discharge, subglottic pressure, blood pressure and instantaneous heart rate, showing an inspiratory facilitatory response with decrease of subglottic pressure and increase of blood pressure and heart rate during electrical stimulation (10mA, 0.4-ms pulses, 50 Hz for 5 s) in the lateral parabrachial nucleus.
known that parabrachial neurones process and transmit tions have also some limitations: do not have any control nociceptive messages. There are recent evidences of of central respiratory activity (tidal volume is studied) and important parabrachial projections to thalamic nuclei in the have been made in spontaneously breathing animals; our rat [2,20,23]. Nociceptive signals may use this parabrachi- group has published data where pontine regulation of al–thalamic pathway to reach specific cortical and other respiration have been studied in artificially ventilated and forebrain sites [20]. Particularly relevant it is the role that paralysed rats [10,25]. The usual volume of our glutamate subnuclei of the lateral parabrachial nucleus plays in pain stimulus was 10 nl (1 nmol) that could spread to a radius transmission [1,2]. Nociceptive effects induced by either ranging from 62 to 225 mm depending also on the electrical or chemical stimulation of the parabrachial characteristics of the the brain tissue [34]. Attending these complex could be present in the described laryngeal and parameters, we think that most of our injections are cardiorespiratory responses as somatic and visceral com- restricted to both the parabrachial complex and the A5
ponents of a nociceptive response. region, although in a few occasions other structures,
¨
The respiratory role of the Kolliker–Fuse nucleus has including trigeminal neurons, could have been activated not yet clearly defined. Chamberlin and Saper [7] have (Fig. 8).
described relevant data regarding respiratory pontine regu- The glottal constriction of the EFR could have both lation but not on laryngeal regulation using smaller physiological or pathological implications. Physiologically, chemical stimuli. They criticize the pneumotaxic role glottal constriction maintains higher lung volumes and this
¨
attributed to the Kolliker–Fuse and medial parabrachial improves gas exchange. Furthermore, this is an important nuclei, suggesting that inhibitory respiratory effects are component of central induced apneas. Complete glottal elicited mainly for activation of trigeminal injections of closure is present throughout most artificially induced glutamate. Most recently, the intertrigeminal region has central apneas in lambs [27]. Glottal constrictions that been describe by the same authors as a region capable of occur during both respiratory phases of the EFR increase driving apneic responses [5]. These important contribu- airway resistance and affect respiratory function. The
Fig. 8. Respiratory rate and subglottic pressure responses to pontine stimulations. Mean changes of respiratory rate and subglottic pressure following ¨
electrical stimulations (h) and glutamate injections (s) in Kolliker–Fuse and medial parabrachial nuclei (A), lateral parabrachial nucleus (B) and A5 region (C).
glottal dilatation of the IFR facilitates, however, respirato- Spanish DGPICYT (PM1999-0163) and by Junta de Andalucia (CTS 0156).
ry movements as a consequence of the decrease of the upper airway resistance.
We have also tested [25] that laryngeal constriction was
References
independent of the cardiovascular change that accom-panied pontine stimulation. Baroreceptor inputs are known
´
[1] H. Bester, L. Menendez, J.M. Besson, J.F. Bernard, Spino
(tri-to inhibit inspira(tri-tory activity and would influence the
gemino) parabrachiohypothalamic pathway: electrophysiological
evi-laryngeal response during the EFR. Pontine activation
dence for an involvement in pain processes, J. Neurophysiol. 73
before and after guanethidine produced a glottal constric- (1995) 568–585.
tion, whilst the rise in blood pressure was abolished by [2] L. Bourgeais, L. Monconduit, L. Villanueva, J.F. Bernard,
Parab-guanethidine. Guanethidine produces a generalised bloc- rachial internal lateral neurons convey nociceptive messages from the deep laminas of the dorsal horn to the intralaminar thalamus, J.
kade of adrenergic activity by acting selectively through
Neurosci. 21 (2001) 2159–2165.
noradrenergic receptors of neurones in peripheric
sympa-[3] C.E. Byrum, P.G. Guyenet, Afferent and efferent connections of the
thetic ganglia. Accordingly, the laryngeal changes were not A5 noradrenergic cell group in the rat, J. Comp. Neurol. 261 (1987) elicited reflexly although the specific blockade action of 529–542.
[4] D.F. Cechetto, D.G. Standaert, C.B. Saper, Spinal and trigeminal
guanethidine on blood pressure cannot exclude that those
dorsal horn projections to the parabrachial nucleus in the rat, J.
responses could be elicited by nociceptive messages
Comp. Neurol. 240 (1985) 153–160.
following parabrachial complex stimulation. [5] N.L. Chamberlin, C.B. Saper, A brainstem network mediating In our previous studies, we have shown that these apneic reflexes in the rat, J. Neurosci. 18 (1998) 6048–6056.
pontine regions can modify the activity of those medullary [6] N.L. Chamberlin, C.B. Saper, Topographic organization of car-diovascular responses to electrical and glutamate microstimulation
respiratory neurones [9,25] that control the respiratory
of the parabrachial nucleus in the rat, J. Comp. Neurol. 326 (1992)
motoneurones. The present observations suggest that the
245–262.
parabrachial complex and the A5 region also have a role in [7] N.L. Chamberlin, C.B. Saper, Topographic organization of respira-modifying the activity of laryngeal motoneurones localised tory responses to glutamate microstimulation of the parabrachial
in the nucleus ambiguous and accordingly the striated nucleus in the rat, J. Neurosci. 14 (1994) 6500–6510.
[8] M.I. Cohen, Switching of the respiratory phases and evoked phrenic
laryngeal muscles of the upper airway. The functional
responses produced by rostral pontine electrical stimulation, J.
interactions between pontine nuclei and laryngeal
Physiol. 217 (1971) 133–158.
motoneurones have not as yet been described neuro- [9] M.S. Dawid Milner, J.P. Lara, S. Gonzalez Baron, K.M. Spyer,´ ´ physiologically but present data are consistent with neuro- Respiratory effects of stimulation of cell bodies of the A5 region in
¨
anatomical observations [3,12,16,17,24,30]. the anaesthetised rat, Pfluger’s Arch.–Eur. J. Physiol. 441 (2001) 434–443.
´
[10] M.S. Dawid-Milner, P. Lopez de Miguel, J.P. Lara, P. Marcos, J.A.
´ ´
Aguirre, S. Gonzalez-Baron, Interactions of A5 region and medial
Acknowledgements parabrachial and Kolliker Fuse nuclei in respiratory and car-´
diovascular control in the anaesthetized rat, J. Physiol. 509 (1998)
[11] T.E. Dick, M.C. Bellingham, D.W. Richter, Pontine respiratory Milner, K.M. Spyer, Cardiovascular and respiratory effects of neurons in anesthetized cats, Brain Res. 636 (1994) 259–269. stimulation of cell bodies of the parabrachial nuclei in the anaesthet-[12] E.G. Dobbins, J.L. Feldman, Brainstem network controlling de- ized rat, J. Physiol. 477 (1994) 321–399.
scending drive to phrenic motoneurons in rat, J. Comp. Neurol. 347 [26] J.P. Lara, M.J. Parkes, K.M. Spyer, The effects of stimulation of the (1994) 64–86. parabrachial complex on the baroreflex in the anaestetized rat, J.
¨
[13] M. Dutschmann, H. Herbert, The Kolliker–Fuse nucleus mediates Physiol. 467 (1993) 19P.
the trigeminally induced apnoea in the rat, NeuroReport 7 (1996) [27] D. Lemaire, P. Letourneau, D. Dorion, J.P. Praud, Complete glottic 1432–1436. closure during central apnea in lambs, J. Otolaryngol. 28 (1999) [14] K. Feil, H. Herbert, Topographic organization of spinal and trigemi- 13–19.
¨
nal somatosensory pathways to the rat parabrachial and Kolliker– [28] A. Mizusawa, H. Ogawa, Y. Kikuchi, W. Hida, K. Shirato, Role of Fuse nuclei, J. Comp. Neurol. 353 (1995) 506–528. the parabrachial nucleus in ventilatory responses of awake rats, J. [15] M.L. Fung, W.M. St. John, Separation of multiple functions in Physiol. 489 (1995) 877–884.
ventilatory control of pneumotaxic mechanisms, Respir. Physiol. 96 [29] Y. Miyaoka, T. Shingai, Y. Takahashi, J. Nakamura, Y. Yamada, (1994) 83–98. Responses of neurons in the parabrachial region of the rat to
˜
´ ´
[16] S.P. Gaytan, F. Calero, P.A. Nunez-Abades, A.M. Morillo, R. electrical stimulation of the superior laryngeal nerve and chemical ´
Pasaro, Pontomedullary efferent projections of the ventral respirato- stimulation of the larynx, Brain Res. Bull. 45 (1998) 95–100. ry neuronal subsets of the rat, Brain Res. Bull. 42 (1997) 323–334. [30] A.M. Morillo, P.A. Nunez Abades, S.P. Gaytan, R. Pasaro, Brain´˜ ´ ´ [17] P.O. Gerrits, G. Holstege, Pontine and medullary projections to the stem projections by axonal collaterals to the rostral and caudal nucleus retroamiguus: a wheat germ agglutinin–horseradish per- ventral respiratory group in the rat, Brain Res. Bull. 37 (1995) oxidase and autoradiographic tracing study in the cat, J. Comp. 205–211.
Neurol. 373 (1996) 173–185. [31] A.M. Motekaitis, I.C. Solomon, M.P. Kaufman, Blockade of gluta-[18] M. Glogowska, A. Stransky, J.G. Widdicombe, Reflex control of mate receptors in CVLM and NTS attenuates airway dilation evoked
discharge in motor fibres of the larynx, J. Physiol. 239 (1974) from parabrachial region, J. Appl. Physiol. 81 (1996) 400–407.
365–381. [32] A.M. Motekaitis, I.C. Solomon, M.P. Kaufman, Stimulation of
´ ´ ´
[19] S. Gonzalez Baron, A. Bogas, M. Molina, F. Garcıa Matilla, Larynx parabrachial nuclei dilates airways in cats, J. Appl. Physiol. 76 resistance and upper airway reflexes, Rev. Esp. Fisiol. 34 (1978) (1994) 1712–1718.
453–462. [33] D. Mutolo, F. Bongianni, M. Carfi, T. Pantaleo, Respiratory
[20] H. Herbert, M.M. Moga, C.B. Saper, Connections of the parabrachi- responses to chemical stimulation of the parabrachial nuclear al nucleus with the nucleus of the solitary tract and the medullary complex in the rabbit, Brain Res. 807 (1998) 182–186.
reticular formation in the rat, J. Comp. Neurol. 293 (1990) 540–580. [34] Ch. Nicholson, Diffusion from an injected volume of a substance in ´
[21] J. Jimenez Vargas, J. Miranda, A. Mouriz, Physiology of the cough: brain tissue with arbitrary volume fraction and tortuosity, Brain Res. differentiation of constrictor and dilatory reflexes of the laryngeal 333 (1985) 325–329.
sphincter, Rev. Esp. Fisiol. 18 (1962) 7–21. [35] J.P. Praud, Larynx and neonatal apneas, Pediatr. Pulmonol. Suppl. [22] J.S. Jodkowski, S.K. Coles, T.E. Dick, Prolongation in expiration 18 (1999) 190–193.
evoked from ventrolateral pons of adult rats, J. Appl. Physiol. 82 [36] W.M. St. John, Respiratory tidal volume responses of cats with (1997) 377–381. chronic pneumotaxic center lesions, Respir. Physiol. 16 (1972) [23] K.E. Krout, A.D. Loewy, Parabrachial nucleus projections to 92–108.
midline and intralaminar thalamic nuclei of the rat, J. Comp. Neurol. [37] A. Stransky, M. Szereda-Przestaszewska, J.G. Widdicombe, The 428 (2000) 475–494. effects of lung reflexes on laryngeal resistance and motoneurone [24] T.L. Krukoff, T.L. Morton, K.H. Harris, J.H. Jhamadas, Expression discharge, J. Physiol. 231 (1973) 417–438.
of c-fos protein in rat brain elicited by electrical stimulation of the [38] G. Paxinos, C. Watson, The Rat Brain in Stereotaxic Coordinates, pontine parabrachial nucleus, J. Neurosci. 12 (1992) 3582–3590. Academic Press, San Diego, CA, USA.
