| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Physiology (2002), 544.1, pp. 183-193
© Copyright 2002 The Physiological Society
DOI: 10.1113/jphysiol.2002.022566
 |
ABSTRACT |
|---|
 TopAbstract IntroductionMethodsResultsDiscussionReferences |
|---|
We aimed in this study to elucidate the discharge properties and neuronal mechanisms of the dissociation between hypoglossal and phrenic inspiratory activities in decerebrate rats, which had been subjected to neuromuscular blockade and artificially ventilated. The discharge of the hypoglossal nerve and the intracellular activity of hypoglossal motoneurones were monitored during respiration and fictive-swallowing evoked by electrical stimulation of the superior laryngeal nerve, and were compared with the activity of the phrenic nerve. The hypoglossal nerve activity was characterized by its onset preceding the phrenic nerve activity ('pre-I' activity). By manipulating artificial respiration, we could augment the 'pre-I' activity, and could elicit another type of hypoglossal activity decoupled from the phrenic-associated inspiratory bursts ('decoupled' activity). We further scrutinized the correlatives of 'pre-I' and 'decoupled' activities in individual hypoglossal motoneurones. Hypoglossal motoneurones consisted of inspiratory (n = 42), expiratory (n = 18) and non-respiratory (n = 1) neurones and were classified by their swallowing activity into depolarized, hyperpolarized, hyperpolarized-depolarized and unresponsive groups. All of the inspiratory neurones were depolarized in accordance with the 'pre-I' and 'decoupled' activities, and all of the expiratory neurones were hyperpolarized during these activities. Fictive swallowing, which was characterized by its frequent emergence just after the phrenic inspiratory activity, was also evoked just after the 'decoupled' hypoglossal activity, suggesting that this activity may have similar effects on swallowing as the 'overt' inspiratory activity. Such a coupling between 'decoupled' and swallowing activities was also revealed in each motoneurone. These findings suggest that the 'pre-I' and 'decoupled' activities may reflect some internal inspiratory activity of the respiratory centre and that hypoglossal motoneurones may be driven by a distinct group of premotor neurones that possibly play a role in the coordination of respiration and swallowing.
(Received 14 April 2002; accepted after revision 4 July 2002; first published online 12 July 2002)
Corresponding author K. Ezure: Department of Neurobiology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashi-dai, Fuchu, Tokyo 183-8526, Japan. Email: ezurek{at}tmin.ac.jp
|
INTRODUCTION |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The onset of inspiratory activity in the hypoglossal (XII) nerve precedes that of the phrenic nerve by several tens of milliseconds under normal conditions (Fukuda & Honda, 1982a; Sica et al. 1984), and this time difference can be markedly prolonged during hypercapnia (Fukuda & Honda, 1988), at the collapse of the pharynx (Hwang & St John, 1987; Ryan et al. 2001) or after vagotomy (Fukuda & Honda, 1982b; Peever et al. 2001). The preceding XII nerve activity may help to maintain the patency of upper airway during the late expiratory phase (Fukuda & Honda, 1988), and the delay of phrenic inspiratory onset assures sufficient expiration in such cases.
Although it is possible that such a temporal difference in inspiratory initiation may merely result from the lower threshold of XII motoneurones and/or the stronger drive placed on them, XII motoneurones and phrenic motoneurones may be influenced differently by the central neuronal network that is involved in the transition from the expiratory to inspiratory phase. To gain further insights, we tried to control the preceding XII nerve activity by manipulating the respirator, and found that certain components of XII nerve activity could be augmented or isolated from the phrenic-associated bursts under various inflation-deflation conditions.
XII nerve activity is used as a monitor of swallowing as well as respiration, and the interaction between the respiratory and swallowing centres is reflected in its discharges (Lowe, 1981; Dick et al. 1993; Ono et al. 1998). Recently we presented data supporting the idea of reciprocal inhibition between respiration and swallowing (Saito et al. 2002). The existence of a type of swallow, which emerges just after the inspiratory phase (termed post-I swallow), well manifests the interaction. In this report we describe that such a coupling is also present between the isolated XII nerve activity mentioned above and the swallowing-related XII nerve activity.
We further confirmed these issues through intracellular recording of individual XII motoneurones, which enabled the elucidation of different patterns of respiration- or swallowing-related drive that cannot be detected by whole or single nerve fibre recording. Based on these findings we discuss the possible segregation of two components of central inspiratory activity in terms of the participation in the initiation of inspiratory activity, as well as in the interaction with swallowing.
|
METHODS |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
All experimental procedures were performed in accordance with the Guiding Principles for the Care and Use of Animals in the Field of Physiological Science (Physiological Society of Japan, 2001). The experiments were reviewed and approved by the Animal Care and Use Committee of the Tokyo Metropolitan Institute for Neuroscience.
Surgical procedure
Experiments were conducted on six adult male rats (355-480 g). The animals were initially anaesthetised with sodium pentobarbitone (Nembutal, 60 mg kg-1; I.P.). Cannulae were placed in the femoral artery and vein for blood pressure monitoring and drug administration, respectively. When necessary, supplementary doses (about 5 mg kg-1 h-1; I.V.) were given throughout surgery before decerebration.
The rats were placed in a stereotaxic frame, initially in the supine position. The XII nerve on one side was cut distally and mounted in a bipolar cuff electrode for both recording and stimulation, and was covered with Vaseline jelly, thin plastic films and skin flaps. The superior laryngeal nerve (SLN) was isolated bilaterally and the distal cut end was tied with a thread. The animals were then rotated to the prone position and supported by hip pins and a clamp placed on an upper thoracic vertebra.
Precollicular decerebration was performed after craniotomy. The brain rostral to the transection was removed by suction. No further anaesthetics were given after decerebration, since this procedure rendered the animals insentient. Partial cerebellectomy was used to expose the dorsal surface of the medulla for recording. The C4/C5 phrenic nerve was cut distally, and was mounted on bipolar recording electrodes and immersed in oil pools, along with the bilateral SLN that was pulled up dorsally. The animals underwent neuromuscular blockade with pancronium bromide (Mioblock, Sankyo, Tokyo; 0.4 mg h-1) and were artificially ventilated. A bilateral pneumothorax was made and a positive end-expiratory pressure (PEEP; 1-3 cmH2O) was applied.
Blood pressure was monitored and kept above 80 mmHg; a pressor agent (10 % dextran, Kobayashi-seiyaku, Tokyo, Japan; 1-2 ml kg-1) was intravenously administered when necessary. End-tidal CO2 was kept below 6 % by adjusting the tidal volume or rate of the respirator. Tracheal pressure and rectal temperature (kept at 36-37 °C) were also monitored.
Recording and stimulation
Activities from the phrenic and XII nerves were amplified, full-wave rectified, and low-pass filtered (
= 10 ms). XII motoneuronal activity was recorded intracellularly with glass micropipettes filled with 2 M potassium citrate-Tris buffer, pH 7.6 (15-20 M
). The XII motoneurones were identified by their antidromic activation from the XII nerve at an intensity ranging from 50 to 200 µA. The location of each recorded unit was measured by using the obex as the reference.
Fictive swallowing could be evoked by electrical stimulation of the SLN with either single pulses, trains of 5-11 pulses at 200-300 Hz, or continuous trains of constant current pulses between 35 and 55 Hz. The intensity of stimulation was between 15 and 60 µA and was less than two-fold the threshold current for phrenic inhibition, which was defined as the current above which the repetitive stimulation of SLN inhibited the central respiratory activity.
All signals of DC amplified membrane potentials, phrenic and XII nerve activities, tracheal pressure and blood pressure were monitored on oscilloscopes and a thermal array recorder (8M15, NEC-Sanei, Tokyo, Japan). In addition, most data were stored on magnetic tape (DAT recorder; PC-216A, Sony Precision Technology, Tokyo, Japan; sampling rate 50 µs) for subsequent off-line analysis.
|
RESULTS |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
XII nerve activity during respiration and swallowing
Under normal ventilatory conditions, both phrenic and XII nerve inspiratory activity started at the nadir and terminated at the peak of tracheal pressure (Fig. 1A). The XII nerve activity preceding that of the phrenic nerve (pre-I XII nerve activity) was markedly exaggerated during periods when this relation was disrupted (Fig. 1B). We found that the exaggerated pre-I XII nerve activity could also be elicited by maintaining lung inflation (Fig. 1C) or by increasing PEEP (Fig. 1E and 1F). In the latter case, the onset of the pre-I XII nerve activity consistently coincided with the nadir of tracheal pressure, but the following 'overt' bursts of phrenic and XII nerve activity started at various timings.
 |
View larger version [in this window] [in a new window] |
|
|
Figure 1. Respiration-related activity of the hypoglossal nerve A, hypoglossal nerve activity during control condition. B and C, exaggerated preceding activity of hypoglossal nerve that appeared spontaneously (B) or was provoked by maintained lung inflation (C). D - F, decoupled type of hypoglossal activity (arrows) that appeared spontaneously (D) and was evoked by increasing PEEP (E and F). XII, integrated hypoglossal nerve activity; Phr, integrated phrenic nerve activity; TP, tracheal pressure. | ||
When the pre-I XII nerve activity was augmented by increased PEEP, a small XII nerve activity that was not followed by an overt burst of phrenic and XII nerve inspiratory activity was often observed (Fig. 1D). In particular, such activities could be easily elicited by larger PEEPs that suppressed overt inspiratory bursts for a prolonged period (Fig. 1F). This small XII nerve activity (decoupled XII nerve activity) that was not accompanied by the overt inspiratory burst always started at the nadir and terminated at the peak of tracheal pressure, but such decoupled activity was never observed during tonic maintained lung inflation.
Fictive swallowing was evoked by SLN stimulation during the period when inspiratory phrenic activity was suppressed ('isolated' swallow)(Fig. 2A), or just after the end of inspiratory phrenic activity (post-I swallow) (Fig. 2B; see Saito et al. 2002). We could also provoke fictive swallowing when the decoupled XII nerve activity was evident (Fig. 2C and D). Notably the 'isolated' swallows that were not coupled with overt bursts of phrenic and XII nerve activity were often preceded by the decoupled XII nerve activity in such cases (Fig. 2C and D). As the decoupled XII nerve activity was terminated during the inflation phase of tracheal pressure, the swallowing-related activity appeared around the peak of tracheal pressure, similar to the pattern of 'post-I' swallows that were provoked just after the termination of the overt bursts of the phrenic and XII nerves.
 |
View larger version [in this window] [in a new window] |
|
|
Figure 2. Swallowing-related activity of hypoglosssal nerve A-D, swallowing (arrowheads) evoked by continuous SLN stimulation at 30-50 Hz (lines over traces). A and B, isolated (A) and post-I (B) rhythmic. C and D, swallowing that occurred just after the decoupled hypoglossal activity (arrows). | ||
Respiration-related activity of XII motoneurones
Intracellular recordings were made from XII motoneurones. Only stable impalements with resting potentials more hyperpolarized than -30 mV (n = 62; range from -30 to -62 mV, average -40 ± 7.1 mV) were included for analysis. These motoneurones were antidromically activated from 0.6-1.6 ms (mean 0.96 ± 0.17) after XII nerve stimulation (Fig. 3A). They were distributed from 1000 µm caudal to 1100 µm rostral to the obex, and from 100-500 µm lateral to the midline. They could be divided into inspiratory (n = 42; Fig. 3B-E), expiratory (n = 19, Fig. 3F; including three neurones with a decrementing pattern of depolarization) and non-respiratory (n = 1) according to their discharge patterns during the respiratory cycle of phrenic nerve discharge.
 |
View larger version [in this window] [in a new window] |
|
|
Figure 3. Respiration-related activity of individual hypoglossal motoneurones A, antidromic potential of the neurone shown in B, evoked by hypoglossal nerve stimulation ( | ||
We were able to observe the behaviour of 36 inspiratory, 13 expiratory and one non-respiratory neurone during the pre-I XII nerve activity that occurred spontaneously (Fig. 3B) or was evoked manually by applying lung inflation (Fig. 3C) or increasing PEEP (Fig. 3D). All of the inspiratory and expiratory neurones were depolarized and hyperpolarized in synchrony with this pre-I component of the XII nerve activity, respectively. In three inspiratory motoneurones, the activity during the preceding inspiratory phase was more intense than the activity during the inspiratory phase (Fig. 3E). The one non-respiratory neurone was not affected during the pre-I period.
As for the decoupled type of XII nerve activity, we were able to examine 25 inspiratory and eight expiratory neurones. The membrane potentials of all inspiratory neurones were depolarized (Fig. 3D and E) and those of all expiratory neurones were hyperpolarized (Fig. 3F) in accordance with the decoupled XII nerve activity.
Swallowing-related activity of XII motoneurones
Both the inspiratory (n = 42) and expiratory (n = 19) motoneurones were classified by their activity during swallowing into depolarized (10 inspiratory and five expiratory; Figs 4A-D, 5A and B), hyperpolarized (16 inspiratory and nine expiratory; Figs 4E, 4F, 5C and 5D), hyperpolarized-depolarized (two inspiratory and one expiratory; Fig. 4G) and unresponsive (16 inspiratory and five expiratory; Fig. 4H and Fig. 5E) neurones. The single non-respiratory neurone (n = 1) was unresponsive to the provocation of swallowing (Fig. 5F). All of the expiratory neurones with a decrementing membrane pattern (n = 3) were depolarized during swallowing (Fig. 5B).
 |
View larger version [in this window] [in a new window] |
|
|
Figure 4. Swallowing-related activity of hypoglossal inspiratory motoneurones A-D, 'depolarization' neurones. E and F, 'hyperpolarization' neurones. G, 'hyperpolarization-depolarization' neurone. H, 'unresponsive' neurone. | ||
 |
View larger version [in this window] [in a new window] |
|
|
Figure 5. Swallowing-related activity of hypoglossal expiratory (A-E) and non-respiratory (F) motoneurones A and B, 'depolarization' neurones. C and D, 'hyperpolarization' neurones. E and F, 'unresponsive' neurones. | ||
In addition, the following variations in activity pattern were observed. Three 'depolarized' inspiratory neurones were characterized by two depolarizing phases during swallowing (Fig. 4C and D). In five 'hyperpolarized' inspiratory neurones, an equivocal depolarization preceded the hyperpolarization (Fig. 4E and F).
Relationship between 'decoupled' and swallowing-related activities in XII motoneurones
When the swallowing emerged just after the decoupled type of XII nerve activity, each motoneurone responded consecutively to both decoupled and swallowing activities. The latter swallowing-related component appeared in the same pattern as the neuronal behaviour during isolated swallowing that was not preceded by the decoupled XII nerve activity (Fig. 6A-C). For example, inspiratory XII motoneurones which were hyperpolarized during swallowing did show a preceding depolarization during the decoupled XII nerve activity and then became hyperpolarized during the ensuing swallow (Fig. 6A). Expiratory motoneurones which were depolarized during swallowing showed a preceding hyperpolarization during the decoupled XII nerve activity and then became depolarized during the ensuing swallow (Fig. 6B). Inspiratory neurones without potential change during swallowing were depolarized during the preceding decoupled XII nerve activity and did not show any apparent change during the ensuing swallow (Fig. 6C).
 |
View larger version [in this window] [in a new window] |
|
|
Figure 6. Coupling between decoupled hypoglossal activity and swallowing-related activity in individual hypoglossal motoneurones A, 'hyperpolarization' inspiratory neurone. B, 'depolarization' expiratory neurone. C, 'unresponsive' inspiratory neurone. | ||
Location of each type of XII motoneurone
We recorded from motoneurones with respiratory activity throughout the length of the XII nucleus. Expiratory neurones predominated in the caudal portion, and inspiratory neurones preponderated in the rostral portion of this nucleus (Fig. 7). Inspiratory and expiratory neurones were intermingled in the middle portion of the XII nucleus.
 |
View larger version [in this window] [in a new window] |
|
|
Figure 7. Distribution of hypoglossal motoneurones with each pattern of respiration- and swallowing-related activity projected on a horizontal plane Open symbols, inspiratory neurone; filled symbols, expiratory neurone; | ||
As for the swallowing-related activity patterns, depolarized neurones were largely concentrated in the middle third of the XII nucleus, and hyperpolarized-depolarized neurones were limited to the area rostral to the obex. In the medial area within 200 µm from the midline, most of the motoneurones were inspiratory and their activity was not affected during swallowing (Fig. 7).
|
DISCUSSION |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Both of the pre-I and decoupled types of XII nerve activity were effectively elicited by changing inputs from lung stretch receptors through the vagal afferents. We think that these activities may not be merely reflex phenomena, but hypothesize that these two types of activities are closely related and may represent certain aspects of central inspiratory activity. In this section we first summarize the nature of respiration- and swallowing-related activities of XII motoneurones, as well as the influence of lung inflation on the pre-I and decoupled types of XII nerve activity, which has been for the first time scrutinized with intracellular recording. Then we discuss the significance of these activities in terms of initiation of inspiration and interaction with the swallowing pattern generator.
Respiration- and swallowing-related activities of XII motoneurones
Some topographical characteristics in the distribution of each XII motoneurone group with a distinct respiratory pattern may be related to the musculotopic arrangement of the subnuclei for the intrinsic and extrinsic tongue muscles. According to anatomical studies (Krammer et al. 1979; Uemura et al. 1979; Uemura-Sumi et al. 1988; Altschuler et al. 1994; Aldes, 1995; Guo et al. 1996), the geniohyoid (GH) motoneurones are located in the most caudal area of this nucleus. 'Expiratory' neurones that predominate in this area (Fig. 7) might correspond to this group of neurones. The significance of the presence and the distribution of expiratory motoneurones remains unclear, because reports to date on this issue are not consistent. Electromyographic studies have shown that the intrinsic and extrinsic tongue muscles are exclusively active during the inspiratory phase (Andrew, 1955; Doty & Bosma, 1956; Fuller et al. 1998). On the other hand, most of the expiratory units in cats (Sumi, 1964; Hwang et al. 1983; Withington-Wary et al. 1988; Ono et al. 1990) are inspiratory-expiratory phase spanning neurones, which we could not detect in the present study. These contradictions may represent species differences or may result from different experimental conditions.
On the other hand, motoneurones innervating the intrinsic tongue muscles are located in the medial subportion of the XII nucleus (Krammer et al. 1979; Uemura-Sumi et al. 1988; Sokoloff & Deacon, 1992; Aldes, 1995). Because intrinsic tongue muscle can show inspiratory activity (Doty & Bosma, 1956), inspiratory neurones in the medial area (Fig. 7) may represent such a population.
The XII motoneurones, similarly to the ambiguus motoneurones (Zoungrana et al. 1997), may be activated or inhibited during the pharyngeal phase of swallowing by the central pattern generator (Jean, 2001) through the premotor neurones in the dorsomedial (Cunningham & Sawchenko, 2000) and ventrolateral (Amri & Car, 1988; Amri et al. 1990; Ezure et al. 1993) reticular formation, or in the perihypoglossal area (Ono et al. 1998), or possibly in the NTS (Saito et al. 2002). Travers & Jackson (1992) reported that the GH and styloglossus (SG) muscles are activated during the early and late phase of swallowing. On the other hand, depolarization-hyperpolarization and depolarization patterns of motoneurones during swallowing are detected in cats, and are attributed to the activity of genioglossus and SG muscles (Tomonoe & Takata, 1988). These may correspond to the hyperpolarization and depolarization groups in the present study, although identification of musculotopic representation remains unclear.
Influence of lung inflation/deflation on the respiratory activity of XII motoneurones
In control conditions, the inspiratory activity of the XII and phrenic nerves started around the nadir, and ceased at the peak of tracheal pressure (Fig. 1A). This represents the disinhibitory and inhibitory actions on the inspiratory activity by inputs from the slowly adapting lung stretch receptors (SARs) through vagal afferents (Cohen, 1969). As to the initiation of the activity, it may also result from facilitation by the rapidly adapting lung stretch receptors (RARs) that are involved in the initiation of augmented inspiration during cough (Widdicombe, 1995) and sigh (Romaniuk et al. 1989) and are facilitated at lung deflation (Ezure & Tanaka, 2000).
In the present study, both pre-I and decoupled XII nerve activities were often conspicuous when the phrenic and XII nerve inspiratory burst, i.e. overt inspiratory burst, did not start at the nadir of tracheal pressure. At that time the pre-I and decoupled XII nerve activities consistently started at the nadir of tracheal pressure. Clearly, the initiation of these XII nerve activities is mediated by phasic inputs from lung stretch receptors; i.e. a facilitatory effect from the RARs or a disinhibitory effect from the SARs, or a combination of both effects may participate in the initiation. In particular, the decoupled XII nerve activity never appeared without the phasic inflation induced by the artificial ventilator, indicating that this rhythmic activity is elicited by the alternative inhibitory and excitatory inputs from lung stretch receptors (Sica et al. 1984; Hwang & St John, 1987; Bartlett & St John, 1988). However, the augmentation of the pre-I XII nerve activity by increasing PEEP or by maintained inflation may not be explained simply by the phasic inputs mentioned above. The augmented pre-I XII nerve activity in vagotomized rats (Fukuda & Honda, 1982b), where the inputs from lung stretch receptors are absent, may not be explained by the stretch receptor-mediated process, either. The augmentation of pre-I activity by increasing PEEP or by maintained inflation may not suggest a facilitatory action of these manoeuvres on the pre-I activity, but may result from the increased inhibitory and decreased excitatory action on the mechanisms that produce overt inspiratory activity of the XII and phrenic nerves.
Without phasic inputs from lung stretch receptors the pre-I XII nerve activity could be initiated probably by some internal drive that develops gradually toward the end of the expiratory phase (see Fig. 1C). A similar drive, in addition to the phasic inputs from lung stretch receptors, seems to operate on the decoupled XII nerve activity (see Fig. 1F). The rhythmic decoupled XII nerve bursts augment gradually toward the end of the expiratory phase and the last burst that fuses into the overt inspiratory activity appears as the pre-I XII nerve activity (see Fig. 1F and Fig. 2D). Based on these observations, we hypothesize that the pre-I and decoupled XII nerve activities have a common drive locked to the late expiratory phase, and that the decoupled activity might represent a modified pre-I activity by the inputs from lung stretch receptors. Indeed, the membrane potential changes of individual motoneurones during the decoupled and pre-I XII nerve activities were in accordance with their respiratory activity. That is, all the motoneurones that were excited during inspiration were also excited during the decoupled and pre-I XII nerve activities, and all the motoneurones that were inhibited during inspiration were also inhibited during the decoupled and pre-I XII nerve activities. This correlation may provide some evidence that these two types of XII nerve activity are related to the central inspiratory activity, which can be regarded as a latent inspiratory activity. This activity might be involved in the central respiratory rhythmogenesis and the interaction between respiration and swallowing, as discussed below.
Segregation of 'phrenic' and 'hypoglossal' types of inspiration in respiratory rhythmogenesis
The pre-I XII nerve activity was suggested to be a consequence of the lower threshold of or stronger inspiratory inputs to XII motoneurones compared to phrenic motoneurones (Sica et al. 1984). However, the hyperpolarization of expiratory XII motoneurones during the pre-I XII nerve activity supports the idea that XII motoneurones receive specific excitatory and inhibitory inputs in synchrony with the pre-I XII nerve activity. It is plausible that phrenic motoneurones or their premotor inspiratory neurones are more strongly inhibited at the late expiratory phase as suggested previously (Fukuda & Honda, 1988). Accordingly, we hypothesize that in the brainstem there are two types of inspiratory neurones: the 'hypoglossal type' and 'phrenic type.' The former presumably include the XII premotor neurones that may discharge during the pre-I XII nerve period, may be influenced differently by chemosensors (Fukuda & Honda, 1982b, 1983, 1988) and lung stretch receptor activities, and may be inhibited to a lesser extent by the expiratory neurones (Fukuda & Honda, 1988; Peever et al. 2001) at the late expiratory phase. In fact, the majority of the augmenting expiratory neurones of the Bötzinger complex (Jiang & Lipski, 1990) are active during the pre-I XII nerve period (K. Ezure, I. Tanaka and Y. Saito, unpublished observations). Their activity may be critical in the suppression of the central inspiratory phase and its initiation.
Actually there are many inspiratory neurones whose firing precedes the overt phrenic burst. Some inspiratory neurones in the ventral respiratory group (VRG) start to fire in the late expiratory phase, and are termed 'expiratory- inspiratory (E-I)' (Cohen, 1969) or 'pre-I-I' (Smith et al. 1990) neurones. On the other hand, some inspiratory neurones in the dorsal respiratory group (DRG), whose discharge is sustained during maintained lung inflation, also start firing preceding the inspiratory phase (Ezure & Tanaka, 2000). Such neurones may include the premotor neurones of the XII motoneurones (Ono et al. 1990; Lipski et al. 1994; Peever et al. 2002), and may provide the respiratory patterns in individual XII motoneurones including the depolarization of inspiratory motoneurones as well as the hyperpolarization of expiratory motoneurones during the pre-I XII nerve period, and possibly during the decoupled XII nerve period. On the other hand, the 'pre-I neurone' suggested by Onimaru et al. (1988) is another type of neurone with discharges preceding the phrenic nerve activity. Because both 'E-I' and 'pre-I' neurones are suggested to be cardinal in respiratory rhythmogenesis (Sun et al. 1998; Ballanyi et al. 1999), the pre-I activity in the XII motoneurones is interesting from this point of view. Therefore, these features of XII nerve activity should be kept in mind when assessing the respiratory function in the brainstem preparation where the XII nerve, in place of the phrenic nerve, is used as a monitor of respiration (Paton et al. 1994).
Interaction between inspiratory and swallowing activities
The interaction between the central pattern generators for swallowing and respiration can be exemplified by the arrest of breathing during swallowing, as well as the predominant emergence of expiration after the completion of swallowing (Selley et al. 1989; Paydarfar et al. 1995). In a recent study we hypothesized a reciprocal inhibition between swallowing and inspiratory activities (Saito et al. 2002). Among others, the observation of post-I swallow (swallow evoked just after the cessation of inspiratory activity) strongly suggested mutual inhibition between inspiration and swallowing.
In the present study, the decoupled XII nerve activity was also shown to couple with swallowing in the same manner as 'real' inspiratory activity. This coupling may result from independent effects of vagal inputs on the swallowing initiation and the decoupled XII nerve activity. Alternatively this coupling can be explained by an inhibitory action on the swallowing initiation from the latent inspiratory activity that drives the decoupled XII nerve activity, and by the disinhibiton of swallowing activity from this drive that is inhibited by lung inflation. From this latter assumption, we hypothesize that the hypoglossal type inspiratory neurones may act on the swallowing pattern generator, while the phrenic type inspiratory neurones may be passively influenced by the same pattern generator. Further examination of the activities of respiratory neurones during the pre-I and decoupled activities and during swallowing may provide a more fundamental view of the interaction between respiration and swallowing.
|
REFERENCES |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
| ALDES, L. D. (1995). Subcompartmental organization of the ventral (protrusor) compartment in the hypoglossal nucleus of the rat. Journal of Comparative Neurology 353, 89-108 | [Medline] |
| ALTSCHULER, S. M., BAO, X. & MISELIS, R. (1994). Dendritic architecture of hypoglossal motoneurons projecting to extrinsic tongue musculature in the rat. Journal of Comparative Neurology 342, 538-550 | [Medline] |
| AMRI, M. & CAR, A. (1988). Projections from the medullary swallowing center to the hypoglossal motor nuclei: a neuroanatomical and electrophysiological study in sheep. Brain Research 441, 119-126 | [Medline] |
| AMRI, M., CAR, A. & ROMAN, C. (1990). Axonal branching of medullary swallowing neurones projecting on the trigeminal and hypoglossal motor nuclei: demonstration by electrophysiological and fluorescent double labeling techniques. Experimental Brain Research 81, 384-390 | [Medline] |
| ANDREW, B. L. (1955). The respiratory displacement of the larynx: a study of the innervation of accessory respiratory muscles. Journal of Physiology 130, 474-487 | |
| BALLANYI, K., ONIMARU, H. & HOMMA, I. (1999). Respiratory network function in the isolated brainstem-spinal cord of newborn rats. Progress in Neurobiology 59, 583-634 | [Medline] |
| BARTLETT, D. & ST JOHN, W. M. (1988). Influence of lung volume on phrenic, hypoglossal and mylohyoid nerve activities. Respiration Physiology 73, 97-110 | [Medline] |
| COHEN, M. I. (1969). Discharge patterns of brain-stem respiratory neurones during Hering-Breuer reflex evoked by lung inflation. Journal of Neurophysiology 32, 356-374 | [Medline] |
| CUNNINGHAM, E. T. JR & SAWCHENKO, P. E. (2000). Dorsal medullary pathways subserving oromotor reflexes in the rat: implications for the central neural control of swallowing. Journal of Comparative Neurology 417, 448-466 | [Medline] |
| DICK, T. E., OKU, Y., ROMANIUK, J. R. & CHERNIACK, N. S. (1993). Interaction between central pattern generators for breathing and swallowing in the cat. Journal of Physiology 465, 715-730 | [Abstract] |
| DOTY, R. W. & BOSMA, J. F. (1956). An electromyographic analysis of reflex deglutition. Journal of Neurophysiology 19, 44-60 | |
| EZURE, K., OKU, Y. & TANAKA, I. (1993). Location and projection of one type of swallowing interneurons in cat medulla. Brain Research 632, 216-224 | [Medline] |
| EZURE, K. & TANAKA, I. (2000). Identification of deflation-sensitive inspiratory neurons in the dorsal respiratory group of the rat. Brain Research 883, 22-30 | [Medline] |
| FUKUDA, Y. & HONDA, Y. (1982a). Differences in respiratory neural activities between vagal (superior laryngeal), hypoglossal and phrenic nerves in the anesthetized rat. Japanese Journal of Physiology 32, 387-398 | [Medline] |
| FUKUDA, Y. & HONDA, Y. (1982b). Roles of vagal afferents on discharge patterns and CO2-responsiveness of efferent superior laryngeal, hypoglossal, and phrenic respiratory activities in anesthetized rats. Japanese Journal of Physiology 32, 689-698 | [Medline] |
| FUKUDA, Y. & HONDA, Y. (1983). Effects of hypocapnia on respiratory timing and inspiratory activities of the superior laryngeal, hypoglossal, and phrenic nerves in the vagotomized rat. Japanese Journal of Physiology 33, 733-742 | [Medline] |
| FUKUDA, Y. & HONDA, Y. (1988). Modification by chemical stimuli of temporal difference in the onset of inspiratory activity between vagal (superior laryngeal) or hypoglossal and phrenic nerves of the rat. Japanese Journal of Physiology 38, 309-319 | [Medline] |
| FULLER, D., MATEIKA, J. H. & FREGOSI, R. F. (1998). Co-activation of tongue protrudor and retractor muscles during chemoreceptor stimulation in the rat. Journal of Physiology 507, 265-276 | [Abstract/Full Text] |
| GUO, Y., GOLDBERG, S. J. & MCCLUNG, J. R. (1996). Compartmental organization of styloglossus and hypoglossus motoneurons in the hypoglossal nucleus of the rat. Brain Research 728, 277-280 | [Medline] |
| HWANG, J.-C., BARTLET, T. D. & ST JOHN, W. M. (1983). Characterization of respiratory-modulated activities of hypoglossal motoneurons. Journal of Applied Physiology 55, 793-798 | [Medline] |
| HWANG, J.-C. & ST JOHN, W. M. (1987). Alterations of hypoglossal motoneuronal activities during pulmonary inflations. Experimental Neurology 97, 615-625 | [Medline] |
| JEAN, A. (2001). Brain stem control of swallowing: neuronal network and cellular mechanisms. Physiological Reveiws 81, 929-969 | |
| JIANG, C. & LIPSKI, J. (1990). Extensive monosynaptic inhibition of ventral respiratory group neurons by augmenting neurones in the Bötzinger complex in the cat. Experimental Brain Research 81, 639-648 | [Medline] |
| KRAMMER, E. B., RATH, T. & LISCHIKA, M. F. (1979). Somatotopic organization of the hypoglossal nucleus: a HRP study in the rat. Brain Research 170, 533-537 | [Medline] |
| LIPSKI, J., ZHANG, X., KRUSZEWSKA, B. & KANJHAN, R. (1994). Morphological study of long axonal projections of ventral medullary inspiratory neurons in the rat. Brain Research 640, 171-184 | [Medline] |
| LOWE, A. A. (1981). The neural regulation of tongue movements. Progress in Neurobiology 15, 295-344 | |
| ONIMARU, H., ARATA, A. & HOMMA, I. (1988). Primary respiratory rhythm generator in the medulla of brainstem-spinal cord preparation from newborn rat. Brain Research 445, 314-324 | [Medline] |
| ONO, T., ISHIKAWA, Y., KURODA, T. & NAKAMURA, Y. (1990). Postspike facilitation of extrinsic tongue muscle activity by respiratory neurones directly projecting to hypoglossal motoneurons. Journal of Dental Research 69, 1057 | |
| ONO, T., ISHIKAWA, Y., KURODA, T. & NAKAMURA, Y. (1998). Swallowing-related perihypoglossal neurons projecting to hypoglossal motoneurons in the cat. Journal of Dental Research 77, 351-360 | [Abstract] |
| PATON, J. F. R., RAMIREZ, J. M. & RICHTER, D. W. (1994). Mechanisms of respiratory rhythm generation change profoundly during early life in mice and rats. Neuroscience Letters 170, 167-170 | [Medline] |
| PAYDARFAR, D., GILBERT, R. J., POPPEL, S. & NASSAB, P. F. (1995). Respiratory phase resetting and airflow changes induced by swallowing in humans. Journal of Physiology 483, 273-288 | [Abstract] |
| PEEVER, J. H., MATEIKA, J. H. & DUFFIN, J. (2001). Respiratory control of hypoglossal motoneurons in the rat. Pflu&guml;ers Archiv 442, 78-86 | [Medline] |
| PEEVER, J. H., SHEN, L. & DUFFIN, J. (2002). Respiratory pre-motor control of hypoglossal motoneurons in the rat. Neuroscience 110, 711-722 | [Medline] |
| ROMANIUK, J. R., BE, W. K., KARCZEWSKI, W. A. & MALINOWSKA, M. (1989). Augmented breath provoked by lung inflation in cat. Acta Neurobiologiae Experimentalis 49, 57-71 | [Medline] |
| RYAN, S., MCNICHOLAS, W. T., O' REGAN, R. G. & NOLAN, P. (2001). Reflex respiratory response to changes in upper airway pressure in the anaesthetized rat. Journal of Physiology 537, 251-265 | [Abstract/Full Text] |
| SAITO, Y., EZURE, K. & TANAKA, I. (2002). Swallowing-related activities of respiratory and non-respiratory neurones in the nucleus of solitary tract in the rat. Journal of Physiology 540, 1047-1060 | [Abstract/Full Text] |
| SELLEY, W. G., FLACK, F. C., ELLIS, R. E. & BROOKS, W. A. (1989). Respiratory patterns associated with swallowing: Part 1. The normal adult pattern and changes with age. Age and Aging 18, 168-172 | |
| SICA, A. L., COHEN, M. I., DONNELLY, D. F. & ZHANG, H. (1984). Hypoglossal motoneuron responses to pulmonary and superior laryngeal afferent inputs. Respiration Physiology 56, 339-357 | [Medline] |
| SMITH, J. C., GREER, J. J., LIU, G. & FELDMAN, J. L. (1990). Neural mechanisms generating respiratory pattern in mammalian brain-stem cord in vitro. Spatiotemporal patterns of motor and medullary neuron activity. Journal of Neurophysiology 64, 1149-1169 | [Abstract] |
| SOKOLOFF, A. J. & DEACON, T. W. (1992). Musculotopic organization of the hypoglossal nucleus in the cynomolgus monkey, Macaca fascicularis. Journal of Comparative Neurology 324, 81-93 | [Medline] |
| SUMI, T. (1964). Neuronal mechanisms in swallowing. Pflügers Archiv 278, 467-477 | |
| SUN, Q.-J., GOODCHILD, A. K., CHALMERS, J. P. & PILOWSKY, P. M. (1998). The pre-Bötzinger complex and phase-spanning neurons in the adult rat. Brain Research 809, 204-213 | [Medline] |
| TOMONOE, N. & TAKATA, M. (1988). Excitatory and inhibitory postsynaptic potentials in cat hypoglossal motoneurons during swallowing. Experimental Brain Research 71, 262-272 | [Medline] |
| TRAVERS, J. B. & JACKSON, L. M. (1992). Hypoglossal neural activity during licking and swallowing in the awake rat. Journal of Neurophysiology 67, 1171-1184 | [Abstract] |
| UEMURA, M., MATSUDA, K., KUME, M., TAKEUCHI, Y., MATSUSHIMA, R. & MIZUNO, N. (1979). Topographical arrangement of hypoglossal motoneurons: an HRP study in the cat. Neuroscience Letters 13, 99-104 | [Medline] |
| UEMURA-SUMI, M., ITOH, M. & MIZUNO, N. (1988). The distribution of hypoglossal motoneurons in the dog, rabbit and rat. Anatomy and Embryology 177, 389-394 | [Medline] |
| WIDDICOMBE, J. G. (1995). Neurophysiology of the cough reflex. European Respiratory Journal 8, 1193-1202 | [Medline] |
| WITHINGTON-WARY, D. J., MIFFLIN, S. W. & SPYER, K. M. (1988). Intracellular analysis of respiratory-modulated hypoglossal motoneurons in the cat. Neuroscience 25, 1041-1051 | [Medline] |
| ZOUNGRANA O. R., AMRI, D. J., CAR, A. & ROMAN, C. (1997). Intracellular activity of the rostral nucleus ambiguus during swallowing in sheep. Journal of Neurophysiology 77, 909-922 | [Abstract/Full Text] |
Acknowledgements
This work was partly supported by a Grant-in-Aid for Scientific Research (for Y.S. and K.E.) from the Japanese Ministry of Education, Culture, Sports, Science and Technology.
This article has been cited by other articles:
|
|
 |
|
  K.-Z. Lee, D. D. Fuller, I-J. Lu, L.-C. Ku, and J.-C. Hwang Pulmonary C-fiber receptor activation abolishes uncoupled facial nerve activity from phrenic bursting during positive end-expired pressure in the rat J Appl Physiol, January 1, 2008; 104(1): 119 - 129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-Z. Lee, D. D. Fuller, L.-C. Tung, I-J. Lu, L.-C. Ku, and J.-C. Hwang Uncoupling of upper airway motor activity from phrenic bursting by positive end-expired pressure in the rat J Appl Physiol, March 1, 2007; 102(3): 878 - 889. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Marchenko and R. F. Rogers Selective loss of high-frequency oscillations in phrenic and hypoglossal activity in the decerebrate rat during gasping Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2006; 291(5): R1414 - R1429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Marchenko and R. F. Rogers Time-frequency coherence analysis of phrenic and hypoglossal activity in the decerebrate rat during eupnea, hyperpnea, and gasping Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2006; 291(5): R1430 - R1442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. M St.-John, J. F. R Paton, and J. C Leiter Uncoupling of rhythmic hypoglossal from phrenic activity in the rat Exp Physiol, November 1, 2004; 89(6): 727 - 737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Duffin Functional organization of respiratory neurones: a brief review of current questions and speculations Exp Physiol, September 1, 2004; 89(5): 517 - 529. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
). Lower trace in A, juxtacellular potential. B-E, inspiratory neurones. F, expiratory neurone. Top trace, intracellular recording.
, non-respiratory neurone. Upward and downward deflection indicates the depolarizing and hyperpolarizing activity changes of each motoneurone during swallowing. Dashed line, contour of the XII nucleus. AP, area postrema; ts, solitary tract.