Respiration Physiology (1988) 73, 189-200 Elsevier
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Respiratory-modulated activities of motor units of the facial nerve Ji-Chuu Hwang and Walter M. St. John Department of Physiology, Dartmouth Medical School, Hanover, Nil 03756, U.S.A. and Department of Biology, National Taiwan Normal University, Ta~ei, 117 Taiwan, Republic of China (Accepted for publication 18 March 1988) Abstract. The purpose of this work was to characterize the influence of activity ofvagal pulmonary receptors upon the discharge pattern of motor units of the facial nerve. Decerebrate and paralyzed cats were ventilated with a servo-respirator which produced pulmonary inflations in parallel with activity of the phrenic nerve. At normocapnia, facial units discharged phasically during neural inspiration, expiration or across both phases or discharged tonically throughout the respiratory cycle. When pulmonary inflation was withheld, the tonic discharge of some units became phasic; others changed the pattern of phasic discharge. In hypercapnia, the number of tonic fiber activities increased and, again, some phasic discharge patterns were altered, Withholding inflation caused similar alterations as in normoeapnia. Activities of facial fibers in vagotomized animals differed in that no tonic activities were recorded, and no change in phasic discharge patterns was induced by hypereapnia. We conclude that afferents from pulmonary stretch receptors influence ventilatory activity throughout the entire respiratory cycle. The concept is discussed that the tonic, as well as phasic discharge of these receptors, is important for the regulation of activity of motoneurons to upper airway muscles.
Cat; Hypercapnia; Phrenic nerve; Pulmonary receptor; Upper airway; Vagus nerve
In a previous study, we have reported the influence of pulmonary inflations upon the respiratory-modulated activity of the buccal branch of the facial nerve (Hwang et al., 1988). We found that phasic inspiratory facial discharge was augmented much more than phrenic activity upon withholding pulmonary inflation. Activity during neural expiration was also augmented when pulmonary inflation was withheld. These influences of pulmonary inflation were qualitatively similar following exposure to hypercapnia or hypoxia; the peak level of facial activity was augmented with these increases in ventilatory drive. In contrast to findings in cats with intact vagi, peak inspiratory facial activity was not significantly increased in hypercapnia or hypoxia following vagotomy (Hwang et al.,
Correspondence address: W.M. St. John, Dept. of Physiology, Dartmouth Medical School, Hanover, NH 03756, U.S.A. 0034-5687/88/$03.50 © 1988 Elsevier Science Publishers B.V. (Biomedical Division)
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1988). However, in vagotomized cats, hypercapnia and hypoxia did cause a significant rise in peak integrated facial activity during expiration. The purpose of the present study was to define the activities of single motor units of the facial nerve which underlay the changes in activity of the facial nerve when vagal pulmonary feedback was removed. The changes, or lack thereof, in activities of facial units upon exposure of animals with intact or sectioned vagi to hypercapnia were also examined. Methods Seven decerebrate cats of either sex were used. The surgical preparation is identical to that described previously (Hwang et aL, 1988). Surgical procedures were performed under halothane, which was discontinued following decerebration. The animal was placed supine. A phrenic nerve and the dorsal buccal branch of the facial nerve were isolated, sectioned and stripped of connective tissue. Massed activity was recorded from the central end of the phrenic nerve. This activity was amplified, electronically filtered (0.6-6.0 kHz) and integrated by a RC circuit. Five animals, having intact vagi, were paralyzed with gallamine triethiodide and ventilated by a 'servo-respirator' (Daubenspeck et aL, 1988; Hwang et aL, 1988). The servo-respirator produced changes in tracheal pressure, and hence lung volume, in parallel with alterations in activity of the phrenic nerve. The volume delivered to the animal was initially adjusted so that the end-tidal partial pressure of CO 2 (FET¢o2) approximated a normocapnic level of 0.05. To produce elevations in FETco:, CO 2 was added to the inspired gas; the end-tidal fractional concentration of 0 2 (FETo:) was always hyperoxic. Tracheal pressure, arterial blood pressure and rectal temperature were continuously monitored and adjusted as described previously (Hwang et al., 1988). Small filaments were dissected from the dorsal buccal branch of the facial nerve. The portion dissected was similar to that from which activity of the whole branch was recorded in Hwang et al. (1988). This portion overlies approximately the rostral half of the maxilla. The filaments of the buccal branch were placed on a bipolar electrode in order to record activities of single units. Pulmonary inflation was withheld to define if activity might be recruited in otherwise inactive filaments. The action potentials were amplified and electronically filtered (0.6 or 1.0 to 6.0 kHz). Activities of the phrenic nerve and single fibers of the facial nerve were recorded on magnetic tape. Pulmonary inflations were periodically withheld for several ventilatory cycles. A minimum of ten cycles with inflations intervened between each set of cycles without inflations. Recordings were obtained at FETco 2 levels of approximately 0.05, 0.06 and 0.09. The vagi were bilaterally sectioned in one of the animals in which vagal pulmonary feedback mechanisms had been evaluated; two other vagotomized cats were also used. These three animals were ventilated with a conventional positive pressure respirator. Activities of single facial motoneurons were recorded at the various FETco 2 levels described above.
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Recordings were played back into a laboratory computer. From records of activity of the phrenic nerve, we determined the durations of the nerve burst (inspiratory duration, TI), the period between bursts (expiratory duration, TE) and the peak integrated height. For facial motor unit activities, the average discharge frequency during each 25 msec of the respiratory cycle was det'med, as was the maximum discharge frequency for each cycle. For animals having intact vagi, activities of the phrenic nerve and facial unit were analyzed for the first ventilatory cycle without inflation and the preceding cycle during which inflation was delivered, At each level of FETco 2 data for equal numbers of respiratory cycles with and without pulmonary inflations were averaged. In vagotomized animals, values for five or more ventilatory cycles were averaged; pulmonary inflations were not withheld. Statistical evaluations were by the non-parametric paired Wilcoxon test, modified for multiple comparisons (Hollander and Wolfe, 1973). Results
I. Animals having intact vagi. Under control conditions with pulmonary inflations at FETco 2 of 0.05, the discharge patterns of the 76 motor units of the facial nerve fell into the following groups: inspiratory (I), expiratory (E), inspiratory-expiratory (I-E), I
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Fig. 3. Numbers of various types of facial motoneuronal activities, recorded at different levels of FEXco2 during ventilatory cycles with and without pulmonary inflations. Three bars above designation of each type of neuronal activity (I, E, I-E, E-I, TONIC, NA) show numbers recorded at FEXco2 levels of 0.05, 0.06 and 0.09 (left to right). NA = units which discharged only after pulmonary inflation had been withheld in hypercapnia. Other abbreviations are as in fig. 1.
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had phasic discharge patterns which commenced, respectively, during neural inspiration or expiration. Tonic units discharged continuously. Concerning these tonic units, 29 of 36 were designated as 'respiratory-modulated' since these consistently exhibited an alteration of discharge frequency during one portion of the ventilatory cycle. Such a consistent alteration was judged by examination of a histogram of the discharge frequency throughout the respiratory cycle (fig. 4). No respiratory modulation of the discharge pattern was evident for the remaining seven tonic fiber activities. However, since one of these units did acquire a respiratory-modulated discharge pattern in hypercapnia, all units having a tonic discharge pattern have been considered as a single group. When pulmonary inflation was withheld, TI, TE, and the peak phrenic height typically increased (figs. 1,2,4). Concomitantly, most fibers maintained the same discharge pattern as when the lungs had been inflated (figs 1,2,4), However, others altered the portion of the ventilatory cycle during which their activity was expressed. Thus, 13 tonic activities were altered to phasic inspiratory (N = 4), inspiratory-expiratory (N = 3) or expiratory-inspiratory (N --- 6). Moreover, some phasic fiber activities were altered A INFLATION
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to different portions of the respiratory cycle. When pulmonary inflation was withheld, six I units became I - E and one discharged tonically; also, four I - E units changed to I and one to a tonic pattern (fig. 1). Withholding pulmonary inflation also resulted in the recruitment of heretofore silent facial fiber activities. Thus, four inspiratory, three expiratory and one inspiratory-expiratory neuron were recruited during the first cycle in which inflation was prevented (fig. 5). The net result of this recruitment of inactive fiber activities and the alteration from tonic to phasic discharges was that the number of fibers having a phasic discharge pattern was greater in ventilatory cycles during which pulmonary inflation was withheld compared to control cycles with inflations (fig. 3). For comparison of alterations in discharge frequency, units were assigned to the groups established during control cycles with pulmonary inflation at FETco 2 of 0.05 (fig. 3). The peak discharge frequencies of the units which had inspiratory or tonic discharge patterns increased significantly when inflation was withheld (fig. 6). Mean values increased for the other groups, although the number of unit activities was not sufficient for statistical evaluations. The augmentation in peak discharge frequencies did not reflect only the prolongation of TI and augmentation of peak inspiratory activity. As shown in fig. 7, the discharge frequency was augmented during much of the inspiratory phase when inflation was withheld. For statistical evaluations, the discharge frequency of inspiratory and tonic units at times equal to 0, 50 and 75 ~/o of the TI for inflation cycles were compared with discharge frequencies at the same number of millisec, during non-inflation cycles. Discharge frequencies were significantly higher at 50 and 75 ~o of TI during cycles without inflation. With progressive elevations of FETco 2 to 0.06 and 0.09, the number of phasic neuronal activities was reduced during cycles with pulmonary inflation (fig. 4). This reduction reflected a conversion to tonic discharge patterns. For example, at FETco 2 of 0.09, tonic discharge patterns were recorded for 7 of 20 neurons which had I discharge patterns at FETco 2of 0.05 and 5 of 7 neurons which had I - E patterns. In addition, some
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Fig. 6. Alterations of peak discharge frequency of various groups of facial motonenrons with elevations of FETCO2. Bars above designation of each type ofnenronal activity (I, E, I-E, E-I, TONIC) show mean values ( + standard errors) for ventilatory cycles with (lei~) and without (right) pulmonary inflations. For this comparison, units were considered as being in the same group as that established by the discharge pattern during cycles with lung inflations at FET¢o 2 of 0.05. * = P < 0.05 compared to cycles with inflation; • • = P < 0.05 compared to values at immediately lower FETco 2. Numbers of units in various groups arc as follows: I = 20, E = 1, I-E = 8, E-I = 1, tonic = 36.
phasic units altered their discharge pattern in hypercapnia. This was especially marked for the I group, three of which became I-E at FETco ~ of 0.06 and one other at FETco z of 0.09. Upon withholding inflation at FET¢o 2 of 0.06 or 0.09, changes in the pattern of discharge were similar to those described above at FETco 2 of 0.05. Thus, the number of units having phasic discharge patterns increased compared to cycles with inflation. However, as noted in fig. 3, the proportion of phasic units during cycles without inflation became progressively lower with elevations of FETco 2. Maximum discharge frequencies were higher during cycles without inflation at all levels of FETco ~ (fig. 6). Likewise, discharge frequencies were significantly higher at 50 and 75 ~ of TI during cycles without inflation. At FETco 2 of 0.06, discharge frequencies were significantly higher for cycles both with and without inflation than at FETco ~ of 0.05. With a further elevation of FETco ~to 0.09, maximum discharge frequencies increased significantly only for cycles with inflation. In addition to the activities of the 76 facial units which were recorded at all levels of FETco 2 examined, activities of an additional 8 units were recorded at one or two levels of FETco 2. The responses of these latter 8 units were as those of the 76 unit activities described above.
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II. Animals having sectioned vagi. Activities of eighteen facial motor units were recorded in cats having bilateral vagal sections. Sixteen of these units discharged in normocapnia; activities in the others were recruited in hypercapnia. The types of phasic motoneuronal activities were as follows: inspiratory (N = 5), expiratory (N = 2), inspiratory-expiratory (N = 1), expiratory-inspiratory (N = 10). One inspiratory and the inspiratory-expiratory discharge were those recruited in hypercapnia. As opposed to recordings in animals having intact vagi, no tonic facial unit activities were recorded. When FETco 2 was elevated from 0.05 to 0.06, the average peak discharge frequency of the entire group of sixteen facial motoneurons, which discharged at both levels of FETco :, increased significantly from 43.5 to 55.8 spikes/sec. The peak discharge frequency at FETco: of 0.09 (57.6 spikes/sec) was not significantly different from that recorded at FETco 2 of 0.06. Finally, in contrast to recordings in animals having intact vagi, no neuronal discharge pattern was altered with elevations of FETco 2.
Discussion
Results of these studies are compatible with the concept that afferent activity from pulmonary stretch receptors is not expressed solely at end-inspiration but throughout the entire respiratory cycle. In addition, our data provide an explanation for the manner
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by which activity of the facial nerve is augmented when pulmonary inflations are prevented. As noted in the preceding companion paper, a number of studies have demonstrated that withholding lung inflation produces a much greater augmentation of activities of the hypoglossal, mylohyoid and facial nerves than of phrenic activity (see Hwang et al., 1988, for references). The manner in which this augmentation is produced is qualitatively similar for phrenic and hypoglossal activities; changes in trigeminal motoneuronal activities have not yet been examined. For both hypoglossal and phrenic motoneurons, the discharge frequencies are increased compared to ventilatory cycles during which the lungs are inflated (Sica et al., 1984; Donnelly et al., 1985; Hwang and St. John, 1987; Hwang etal., 1987). Although some motoneuronal activities, especially hypoglossal units, are recruited when inflations are withheld, the great majority of neurons do not change the portion of the respiratory cycle in which these are active. Augmentations in discharge frequency of both phasic and tonic facial fibers account, in part, for increases in peak inspiratory and expiratory activities of the facial nerve when lung inflations were withheld. However, a contribution to this augmentation in peak activities may be the switch from tonic to phasic discharge patterns, combined with the increase in discharge frequency. Concerning augmentations in discharge frequency, these were evident throughout the inspiratory phase when pulmonary inflation was withheld. This finding provides support for the concept that influences from pulmonary stretch receptors must be expressed throughout the entire inspiratory phase (see Hwang and St. John, 1987, for discussion). In addition, our results demonstrate that lung inflation during inspiration may alter activity during the subsequent expiratory phase. As noted in Results, the discharge frequency and/or firing pattern during expiration of many facial motor neurons were altered when pulmonary inflation was prevented. These changes during expiration might reflect differences in lung volume, and the discharge of pulmonary stretch receptors, for cycles with and without inflation. Since the lungs do not immediately return to the functional residual capacity after inflation, receptors might continue to discharge in early neural expiration (see Hwang and St. John, 1987, for full discussion). The well-documented relationship between inspiratory and expiratory activities, which is defined by processes inherent to the brainstem respiratory control system (e.g., Cohen, 1979; Euler, 1986), might also account for the influence of pulmonary inflations upon expiratory activities. Another influence upon these expiratory activities might be the tonic discharge of pulmonary stretch receptors. Indeed, the differences between discharge patterns of facial motor units in cats having intact and sectioned vagi provide additional strong evidence that the tonic discharge of vagal pulmonary receptors significantly influences ventilatory activity (Coleridge and Coleridge, 1986, pp. 407-413). As noted in Results, withholding pulmonary inflation and sectioning of the vagi were not equivalent in inducing alterations of facial motor unit activities. In the vagotomized animal, the absence of all tonic facial motoneuronal activities and the lack of any hypercapnia-induced change in discharge pattern of these motoneurons contrast with the findings when inflation was withheld in animals having intact vagi. During this latter
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procedure, many tonic activities were recorded and hypercapnia changed the periods of activity of many phasic neurons. It is extremely improbable that the absence of any tonic facial activities in the vagotomized animal could reflect a problem of sampling. In animals having intact vagi, 23 of 76 facial units had tonic discharge patterns during cycles without inflation at FETco: of 0.05. Hence, the probability that any given unit would have a tonic discharge was approximately 0.30. The probability that no tonic fiber activities would be found in a sample of 18 units in the vagotomized animal is thus 0.30 x 10TM. In addition to activities of facial motor units, another difference between withholding pulmonary inflation and vagotomy has been noted in regard to the discharge pattern of the facial nerve and the changes in this neural activity in hypercapnia (Hwang et al., 1988). Concerning hypercapnia-induced changes, an unexpected finding in the present study was that, in animals having intact vagi, the number of facial motor units having tonic discharge patterns increased as the end-tidal fractional concentration of CO2 was elevated. This increase in the number of tonic neuronal activities was observed both for cycles in which the lungs were inflated and those during which no inflation was delivered. As was discussed above for responses during normocapnia, lung inflation caused more neurons to assume tonic discharge patterns at any level of FETco 2. The hypercapnia-induced switch of facial motoneuronal activities from phasic to tonic patterns was unexpected since hypercapnia resulted in directly opposite changes in all other types of respiratory-modulated neuronal activities which have previously been examined. Thus, in vagotomized animals, elevations of FETco 2 from hypocapnic or normocapnic to hypercapnic levels cause many medullary and pontile units, having tonic discharge patterns, to discharge phasically (Cohen, 1968; Fallert etal., 1977; St. John and Wang, 1977; Bianchi and St. John, 1982; St. John and Bianchi, 1985). Exclusive of the procedure of maintaining animals in hypercapnia in some studies, to our knowledge only a recent study in this laboratory has specifically considered the interaction of lung inflation and hypercapnia in defining the discharge patterns of brainstem respiratory neurons. In this study (St. John, 1987), the very great majority of rostral pontile neurons maintained the same phasic or tonic respiratory-modulated discharge patterns independent of the presence or absence of pulmonary inflation or level of FETco 2. An exception to this absence of change was the observation that approximately 13~o of the tonic respiratory-modulated neuronal activities became phasic when pulmonary inflation was withheld; there was no discernible influence of hypercapnia on this response. In this context, Feldman et al. (1976) found that few rostral pontile neurons had any respiratory-modulated discharge pattern except when puhnonary inflation was prevented. In the recent study considered above (St. John, 1987), these findings of Feldman et al. (1976) were not confirmed. Two interrelated points remain to be discussed. The first concerns the possibility that some of the fiber activities that we recorded were fusimotor rather than alpha. While we cannot eliminate this possibility, the much greater amplitude of action potentials in alpha, as compared to fusimotor fibers (e.g., Sears, 1964), makes it highly probably that most recordings were of alpha fibers.
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The second point concerns the specific muscle groups which were innervated by the axons from which activity was recorded. As noted in Methods, activities were recorded from the rostral portion of the dorsal buccal branch of the facial nerve. Hence, most of the axons would have innervated the procerus, nasalis and depressor septi muscles of the nose. However, it is also possible that some of these axons would have innervated muscles of the orbicularis otis of the mouth, especially those on dorsal surface of the lips (Goss, 1973). In summary, the results reported herein for facial motor unit activities, in the presence and absence of pulmonary inflations and intact vagus nerves, demonstrate that vagal afferents exert both phasic and tonic influences upon ventilatory activity. Thus, these vagal influences elicit much more complex changes in activities within the brainstem respiratory control system than an 'all-or-none' inhibition of inspiratory activity (Euler, 1986).
Acknowledgements.These studies were supported by grant 20574 from the National Heart, Lung and Blood Institute, National Institutes of Health and grant NSC 76-0201-B003-06 from the National Science Council, Republic of China. The technical assistance of Kurt V. Knuth and Dale Ward is gratefully acknowledged, We thank Dr. Donald Bartlett for his helpful comments concerning this manuscript.
References Bianchi, A.L. and W.M. St. John (1982). Medullary axonal projections of respiratory neurons of pontile pneumotaxic center. Respir. Physiol. 45: 167-183. Cohen, M.I. (1968). Discharge pattern of brain-stem respiratory neurons in relation to carbon dioxide tension. J. Neurophysiol. 31: 148-165. Cohen, M.I. (1979). Neurogenesis of respiratory rhythm in the mammal. Physiol. Rev. 59: 1105-1173. Coleridge, H.M. and J. C. G. Coleridge (1986). Reflexes evoked from tracheobronchial tree and lungs. In: Handbook of Physiology. Section 3. The Respiratory System. Vol. II. Part I, edited by A. P. Fishman. Bethesda, MD, American Physiological Society, pp. 407-413. Daubenspeck, J. A., D. Pichon, D. Bartlett, Jr. and W.M. St. John (1988). An inexpensive servo-respirator based upon regulation of a shunt resistance. Respir. Physiol. 73: 87-96. Donnelly, D.F., M.I. Cohen, A.L. Sica and H. Zhang (1985). Responses of early and late onset phrenic motoneurons to lung inflation. Respir. Physiol. 61: 69-83. Euler, C. von (1986). Brain stem mechanisms for generation and control of breathing pattern. In: Handbook of Physiology. The Respiratory System. Vol. II. Part I, edited by A.P. Fishman. Bethesda, MD, American Physiological Society, pp. 25-54. Fallert, M., G. Bohmer and H.R.O. Dinse (1977). Patterns of bulbar respiratory neurons during and after artificial hyperventilation. Respir. Physiol. 29: 143-149. Feldman, J. L., M.I. Cohen and P. Wolotsky (1976). Powerful inhibition of pontine respiratory neurons by pulmonary afferent activity. Brain Res. 104: 341-346. Goss, C. M. (1973). Anatomy of the Human Body by Henry Gray. Philadelphia, Lea & Fegier, pp. 382-386. Hollander, M. and D. A. Wolfe (1973). Nonparametric Statistical Methods. New York, Wiley, pp. 171-178. Hwang, J.-C. and W.M. St. John (1987). Alterations of hypoglossal motoneuronal activities during pulmonary inflations. Exp. Neurol. 97: 615-625. Hwang, J.-C., W.M. St. John and D. Bartlett, Jr. (1987). Influence of pulmonary inflations upon discharge patterns of phrenic motoneurons. J. Appl. Physiol. 63: 1421-1427.
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Hwang, J.-C., C.-T. Chien and W. M. St. John (1988). Characterization of respiratory-related activity of the facial nerve. Respir. Physiol. 73: 175-188. Sears, T.A. (1964). Efferent discharges in alpha and fusimotor fibres of intercostal nerves of the cat. J. Physiol. (London) 174: 295-315. Sica, A.I., M.I. Cohen, D.F. Donnelly and H. Zhang (1984). Hypoglossal motoneuron responses to pulmonary and superior laryngeal afferent inputs. Respir. Physiol. 56: 339-357. St. John, W.M. and S.C. Wang (1977). Response of medullary respiratory neurons to hypercapnia and isocapnic hypoxia. J. Appl. Physiol. 43: 812-822. St. John, W.M. and A.L. Bianchi (1985). Responses of bulbospinal and laryngeal respiratory neurons to hypercapnia and hypoxia. J. Appl. Physiol. 59: 1201-1207. St. John, W. M. (1987). Influence of pulmonary inflations upon discharge of pontile respiratory neurons. J. Appl. Physiol. 62: 2231-2239.