Hypoglossal Activity Research Articles

Hypoglossal responses to macular stimulation in the rabbit

This paper describes preliminary work on the role of the vestibular system in the hypoglossal neurons modulation. Natural stimulation of the otolith organ showed that hypoglossal motoneurons are responsive to gravity stimulation. The spontaneous firing rate of single cells, antidromically identified, was significantly modified during ipsi- or contralateral static tilting of the whole animal. Several response patterns were observed. These results infer that vestibular macular receptors may modulate hypoglossal nucleus activity in response to static head displacement.

Influence of reticular mechanisms upon hypoglossal, trigeminal and phrenic activiteis

Studies were undertaken to evaluate the hypothesis that mechanims within the reticular formation influence activities of nerves to muscles of the upper airways more than the bulbospina-phrenic system. In decerebrate, vagotomized, paralyzed and ventilated cats, activities of the phrenic, trigeminal, and the hypoglossal nerves were monitores. Activity of the pontile and medullary reticular formation was increased directly by electrical stimulation within the brainstem and indirectly by stimulating the sciatic nerve. Trigeminal and hypoglossal discharges increased more than phrenic during stimulating at many brainstem loci. Changes were typically maintained for one or more respiratory cycles following termination of stimulation. At some loci, activation of neurons by microinjections of glutamate increased trigeminal and hypoglossal activities more than phrenic. Although responses were extremely variable, activities of the trigeminal and/or hypoglossal nerves usually increased more than phrenic during stimulations of the sciatic nerve or upon termination of stimulation. The result support the conclusion that respiratory-modulated trigeminal and hypopglossal discharges are dependent upon reticular mechanimss for their expression.

Comparison of the effects of hypercapnia on phrenic and hypoglossal activity in anesthetized decerebrate and decorticate animals

To examine the effects of suprapontine structures on the activity of hypoglossal and phrenic nerves, 13 chloralose anesthetized, paralyzed (gallamine triethiodide) and artificially ventilated cats were studied. In all animals vagi and carotid sinus nerves were cut bilaterally. All animals were first hyperventilated to apnea and then made progressively hypercapnic by rebreathing under hyperoxic conditions. Following midcollicular decerebration, the peak phasic activity of the hypoglossal nerve was significantly depressed and the PCO 2 at which apnea occurred (apneic point) increased. However, following high decerebration or decortication the activity of the hypoglossal nerve was increased at higher CO 2 levels and there was no change in apneic point. By contrast, peak phrenic nerve activity was not altered by any of the above surgical procedures. Neither systemic blood pressure nor respiratory frequency were significantly altered by these procedures. The results indicate that suprapontine structures can appreciably modify hypoglossal activity.

DIFFERENCES IN THE EFFECTS OF HYPERCAPNIA AND HYPOXIA ON THE SWALLOWING REFLEX IN CATS

The effects of changes in PaCO2 and PaO2 on the swallowing reflex were studied in anaesthetized, vagotomized, paralysed and artificially ventilated cats. The swallowing reflex was induced by electrical stimulation of the superior laryngeal nerve (SLN). This initially suppressed activity in the phrenic nerve (PN). The swallowing reflex was then identified by a characteristic brief burst of PN activity and a large amplitude burst of hypoglossal nerve (HN) activity. Steady-state responses to constant SLN stimulation for 60 s were measured at four carbon dioxide tensions (PaCO2 3.9, 5.1, 6.3 and 7.8 kPa) with hyperoxia (PaO2 greater than 51 kPa) and at four values of PaO2 (PaO2 56, 11.3, 6.9 and 4.8 kPa) at a fixed PaCO2 (PaCO2 4.2 kPa). Although both hypercapnia and hypoxia increased the spontaneous respiratory activity in PN and HN, the number of swallows elicited during SLN stimulation was not influenced by PaCO2, whereas a progressive decrease in the number of swallows with decreasing PaO2 was observed consistently. These results indicate that the swallowing reflex is independent of the background respiratory activity and that hypoxia depresses the swallowing reflex, whereas hypercapnia has no effect.

Influence of morphine on respiratory activities of phrenic and hypoglossal nerves in cats

Anesthetic and sedative drugs have been found to diminish the respiratory motor activity of the hypoglossal nerve more than that of the phrenic nerve. This differential depression of motor activity to the upper airway may contribute to the exacerbation of obstructive sleep apnea by sedative drugs. To determine whether morphine has a similar selective action, we recorded phrenic and hypoglossal nerve activities before and after morphine administration in decebrate, vagotomized cats, paralyzed with gallamine. Morphine diminished the activities of both nerves in most animals, but the responses were highly variable, and no consistent pattern of differential depression was apparent. The variability of the results may reflect the complex nature of opiate actions on the control of breathing.

Inhibition of inspiratory upper airway motoneuron activity by phasic volume feedback.

The effects of phasic volume feedback on efferent hypoglossal, recurrent laryngeal and phrenic nerve activity were studied in decerebrate, paralyzed intubated cats ventilated with a phrenic-driven servo-respirator. The gain of the respirator was altered for single inspirations, and the resulting changes in neural activities were quantified by comparison with respective neural activities without phasic volume feedback. The volume thresholds for suppression of hypoglossal and recurrent laryngeal activities were time independent. Above these two thresholds and extending over a substantial range, volume feedback caused graded inhibition of upper airway motoneuron outputs. At any particular time during inspiration the relationships between hypoglossal or recurrent laryngeal inhibition and volume were concave to the volume axis. Rate of airflow appeared to exert an effect on upper airway motoneuron activity independent of volume. These results indicate that for hypoglossal and recurrent laryngeal efferent activity 1) volume feedback can cause a sustained graded inhibition throughout inspiration; 2) the volume thresholds are time independent; and 3) partial inhibition decreases susceptibility to additional inhibition. These actions of volume feedback on upper airway motoneuron output differ from those on phrenic efferent discharge and show that phasic vagal volume feedback has a marked and differential effect on upper airway motoneuron activity. The vagus, in this preparation, appears to play a critical role in the regulation of upper airway motoneuron activity and therefore maintenance of upper airway patency.

Differential depression of hypoglossal nerve activity by alcohol. Protection by pretreatment with medroxyprogesterone acetate.

Upper airway obstruction during sleep occurs more commonly in men than in women and has been treated with progestational agents with some success. Alcohol ingestion exacerbates sleep apnea, and recent studies have established that alcohol depresses the respiratory motor activity to upper airway muscles more than that to the diaphragm, a response pattern that favors upper airway obstruction during inspiration. To investigate the possibility that progesterone provides some protection from this action of alcohol, we studied the responses of phrenic and hypoglossal nerve activities to alcohol infusion in decerebrate cats pretreated with medroxyprogesterone acetate (MPA) or with control injections. The results indicate that pretreatment with MPA reduces the alcohol-induced mismatching of hypoglossal and phrenic activities. This action of MPA may contribute to its effectiveness in the treatment of some patients with inspiratory obstruction during sleep.

Vestibular ampullar modulation of hypoglossal neurons

This paper describes preliminary observations on vestibular ampullar involvement in the control mechanism of the hypoglossal nucleus activity. Thermic stimulation of the labyrinth, performed by irrigating the external auditory meatus with cold water (20°C), significantly modified the spontaneous electrical activity of hypoglossal neurons localized in the medio-caudal part of the nucleus. Tonic spontaneous discharge of the units following labyrinthine stimulation was modified into a phasic activity and bursts with multi-unit recruitment appeared. This modified activity was observed during 5–6 minutes after the onset of ear irrigation. Similar response patterns, but with shorter duration, were recorded following contralateral stimulation of the labyrinth. These results show that hypoglossal neurons are triggered by the vestibular system following dynamic conditions in response to every spatial head displacement.

Comparison of respiratory-related trigeminal, hypoglossal and phrenic activities

In decerebrate, paralyzed and vagotomized cats, we recorded activities of hypoglossal and phrenic nerves and of the mylohyoid branch of the trigeminal nerve. At normocapnia, a respiratory-modulated trigeminal discharge could be discrened in most cats. This discharge was characterized by a diminution of activity during neural inspiration and a peak in expiration. In hypercapnia or hypoxia, peak activity increased and its time of occurence moved to late inspiration. Augmentations of peak trigeminal, hypoglossal and phrenic activities were proportional. Peak trigeminal and hypoglossal activities increased more than phrenic following administration of protriptyline, strychnine and, in some cats, cyanide or doxapram. Peak trigeminal activity fell more than phrenic after diazepam. Pentobarbital or halothane reduced peak hypoglossal, but not trigeminal, activity more than phrenic. However, after these anesthetics, trigeminal activity became restricted to the inspiratory-expiratory junction. We conclude that trigeminal and hypoglossal activities are more dependent upon processes within the retcicular formation than in the bulbospinal-phrenic system. Central and peripheral chemoreceptor influences are distributed equivalently upon trigeminal, hypoglossal and phrenic motoneurons.

The effects of hypercapnia and cooling the ventral medullary surface on capsaicin induced respiratory reflexes

The effect of right atrial (RA) injection of 3 μg/kg capsaicin on phrenic, hypoglossal and recurrent laryngeal activities was studied in chloralose anesthetized, paralyzed and artificially ventilated cats. Within 2 sec following capsaicin injection, the phrenic and hypoglossal activities completely disappeared (apnea), while the recurrent laryngeal activity markedly increased. Similar responses were also obtained with RA injection of phenyldiguinide (PDG), suggesting that the respiratory responses of both drugs are essentially similar. Sino-aortic denervation did not affect the capsaicin induced respiratory responses. Bilateral vagotomy abolished the responses, suggesting that vagal sensory receptors are responsible for the reflex effects. Hyperoxic hypercapnia (3 and 7% CO 2 in O 2) reduced the apneic duration of phrenic and hypoglossal nerves. The magnitude of the recurrent laryngeal excitation was decreased during CO 2 breathing. Graded focal cooling of the intermediate area (I S area) of the ventral medullary surface (to inhibit central chemoreceptor activity) significantly prolonged capsaicin induced apneic duration of hypoglossal nerves more than the phrenic. The recurrent laryngeal responses, however, were unaffected by cooling of the ventral medullary surface. The results show that capsaicin and PDG, presumably by stimulating C fibers, affect cranial nerves as well as the phrenic. The reflex responses to C fiber stimulation seem to be altered by intervention which stimulate (hypercapnia) or depress (I S cooling) ‘central chemoreceptors’.

EFFECTS OF INCREASING DEPTH OF ANAESTHESIA ON PHRENIC NERVE AND HYPOGLOSSAL NERVE ACTIVITY DURING THE SWALLOWING REFLEX IN CATS

The effects of increasing depths of anaesthesia on phrenic nerve (PN) activity and hypoglossal nerve (HN) activity during the swallowing reflex elicited by stimulation of the superior laryngeal nerve (SLN) were investigated in 10 cats. Swallowing induced by SLN stimulation always coincided with a characteristic brief burst of PN activity and a large amplitude burst of HN activity. These characteristic responses of PN and HN activities were not influenced by either bilateral vagotomy or neuromuscular blockade, indicating that the characteristic responses of PN and HN activities can be used as indicators of the swallowing reflex in vagotomized and paralysed animals. The results obtained in such animals showed that increasing depth of anaesthesia depressed progressively the swallowing reflex. Detailed analysis of HN activity revealed also that SLN stimulation elicited three different responses of HN activity which had different sensitivities to anaesthesia. However, the characteristic response observed during the swallowing reflex was the most sensitive to increasing depth of anaesthesia.

Differential elevation by protriptyline and depression by diazepam of upper airway respiratory motor activity.

Effects of systemically administered protriptyline and diazepam on the respiratory activity of the phrenic, hypoglossal, and recurrent laryngeal nerves were investigated in vagotomized, decerebrate cats. Both hypoglossal and recurrent laryngeal nerve activities were consistently increased after protriptyline administration, whereas the phrenic nerve discharge was not systematically altered. Similar changes were observed in cats with bilateral carotid sinus nerve sections. Diazepam induced a reduction of hypoglossal and recurrent laryngeal nerve activities at doses that did not alter phrenic nerve discharge. These results with diazepam were the same in carotid chemodenervated cats. We conclude that neural mechanisms controlling upper airway muscles are much more sensitive to protriptyline and diazepam than are those of the bulbospinal-phrenic system. The selective augmentation of hypoglossal and recurrent laryngeal discharges by protriptyline could account for the reported decrease in the frequency of obstructive sleep apneas in patients receiving this antidepressant. In contrast, diazepam, by depressing motor activity to upper airway muscles, may exacerbate oropharyngeal obstruction during sleep.

Peripheral influences on the central pattern-rhythm generator for tongue movements in the rat

Rhythmic activity in the tongue and other oral muscles was evoked by mechanical stimulation of the hard palate in ketamine-anaesthetized rats. The relation between neural discharges of single hypoglossal motoneurones and activity in the masseter and anterior digastric muscle, and stimulus parameters was analysed. By varying the stimulus parameters, hypoglossal-motoneurone activity was modulated from phasic reflex activity into rhythmic activity. The tongue and other recorded muscles are likely to be controlled by the same pattern-rhythm generator, when rhythmic activity is induced by palatal stimulation. Exteroceptive oral stimuli can activate the tongue pattern-rhythm generator independently of proprioceptive feedback. Proprioceptive input from oral structures influenced the burst duration of rhythmic hypoglossal motoneurone activity. The cycle duration and the number of discharges/burst, however, was not affected by proprioceptive input. The hypoglossal-motoneurone pool may be influenced by more than one pattern-rhythm generator because the burst characteristics of rhythmically-firing hypoglossal motoneurones depend upon stimulus conditions. These hypoglossal pattern-rhythm generators have possible hierarchic relations because a shift from one burst pattern into another can be evoked by changing stimulus conditions. The pattern-rhythm generators for oral movements may be composed of a neural-pattern generator and a neural-rhythm generator, which can be modulated separately by peripheral inputs.

Action of nicotine on the respiratory activity of the diaphragm and genioglossus muscles and the nerves that innervate them

Nicotine is known to alter respiration by stimulating peripheral chemoreceptors and receptors within the brain. In this study the sites of action and the effects of nicotine on hypoglossal nerve activity were compared to its effects on phrenic activity in paralyzed, vagotomized and chloralose-anesthetized cats. Since anesthesia is known to affect respiratory responses, we also compared the effects of intravenous nicotine given to conscious unsedated cats on genioglossus and diaphragm electrical activity. In eight conscious animals intravenous doses of nicotine ranging between 10 ng and 200 μg increased genioglossus activity significantly more than diaphragm activity. Studies in 26 anesthetized animals included injection of nicotine, intravenously, in the lateral ventricles, and application of nicotine to the ventrolateral surface of the medulla (the putative site of the central chemoreceptors) before and after section of the carotid sinus nerves. With all these interventions, changes in hypoglossal nerve activity were significantly greater than changes in phrenic nerve activity. The responses to nicotine could be blocked by application of hexamethonium to the ventrolateral medullary surface of by cooling the same area. The results indicate that: nicotine increases hypoglossal nerve activity by both its peripheral and central effects; nicotine has differential effects on different respiratory muscles and nerves; and the central action of nicotine may be mediated largely through receptors located near the ventral medullary surface.

Anesthesia selectively reduces hypoglossal nerve activity by actions upon the brain stem.

Alcohol as well as anesthetic and sedative agents depress the respiratory activity of the hypoglossal-genioglossal system more than that of the phrenic-diaphragmatic system. The mechanisms for this selective depression remain unclear. To evaluate the contribution of pathways traversing the spinal cord, the response of phrenic and hypoglossal nerve activities to 0.5% halothane was obtained in decerebrate cats before and after transection of the spinal cord at T1 and again following transection at C1. Halothane produced a much greater decrease in hypoglossal than phrenic activity before and after spinal cord section at T1. Following cord section at C1, which eliminates phrenic activity, 0.5% halothane still produced a marked depression of hypoglossal activity. Therefore, the selective depression of the hypoglossal-genioglossal system does not depend on spinal mechanisms and appears to be mediated in the brain stem.

Selective depression by ethanol of upper airway respiratory motor activity in cats.

We studied the effects of systemically administered ethyl alcohol on the respiratory motor activity of the phrenic, hypoglossal and recurrent laryngeal nerves in unanesthetized, decerebrate cats. Some of the cats were studied after carotid sinus nerve section. In addition, parallel studies were done in intact, awake cats with chronic electromyographic electrodes in the diaphragm, genioglossus, and posterior cricoarytenoid (PCA) muscles. In decerebrate animals, alcohol induced a significant reduction of hypoglossal and recurrent laryngeal nerve activities at doses that had little or no effect on the phrenic nerve discharge. Similar changes were observed in chemodenervated cats. In awake animals, genioglossal and PCA muscle activities were depressed by alcohol, whereas diaphragm activity showed no consistent change. Alcohol caused a significant increase in respiratory frequency in awake cats and reduced the responses of genioglossal and PCA muscle activities to hypercapnia and normocapnic hypoxia. We conclude that alcohol induces a selective reduction in upper airway respiratory motor activity by an action that does not require intact suprapontile structures, vagal afferents, or peripheral chemoreceptors. This reduction may contribute to the alcohol-induced exacerbation of obstructive sleep apnea.

Hypoglossal motoneuron responses to pulmonary and superior laryngeal afferent inputs

In decerebrate, paralyzed cats ventilated with a cycle-triggered pump, the inspiratory discharges of the hypoglossal (whole nerve or single fibers), phrenic, and recurrent laryngeal nerves were compared, and the effects of pulmonary and superior laryngeal inputs were observed. During lung inflations phase with neural inspiration, hypoglossal and recurrent laryngeal activities differed from phrenic with respect to (a) burst onset times: both preceded the phrenic; (b) overall pattern: phrenic, augmenting; hypoglossal, decrementing; recurrent laryngeal, plateau-like. When inflation was withheld, the phrenic pattern was not markedly changed, but both hypoglossal and recurrent laryngeal became augmenting; the marked increas of hypoglossal activity (both whole nerve and single fiber) indicated strong inhibition by lung afferents. Superior laryngeal electrical stimulation evoked excitation of the contralateral phrenic (latency 4.1 msec) and the ipsilateral whole hypoglossal (latency 5.3 msec), followed by bilateral inhibitions (durations 20–30 msec); most hypoglossal fibers showed only inhibition. We conclude that, although both hypoglossal and phrenic outputs are driven by the inspiratory pattern generator(s), their premotor systems differ with respect to influences from central and peripheral inputs.

Dynamic changes of hypoglossal and phrenic activities by hypoxia and hypercapnia

Steady-state responses of unanesthetized subjects to hypercapnia of hypoxia provide no evidence that chemoreceptor afferents are differentially distributed upon hypoglossal and busbospinal-phrenic neurons, as suggested by results in anesthetized animals. We hypothesized that dynamic changes in activities of phrenic and hypoglossal nerves might differ following sudden alterations of inspired gases. This hypothesis was based on the observation that episodes of obstructive apnea may follow central apnea. The obstruction might reflect phrenic activity increasing more quickly than that of the hypoglossal upon resumption of ventilation. In decerebrate, vagotomized, paralyzed and ventilated cats, we recorded phrenic and hypoglossal activities before and during abrupt, sustained exposure to hypocapnia, hypoxia and hypoxic hypocapnia, and following sudden withdrawal of these stimuli. For all such manoeuvres, activities of phrenic and hypoglossal nerves incresed or decreased in parallel fashion. Our findings rejection of the hypothesis of differing dynamic phrenic and hypoglossal responses to chemoreceptor stimuli. The concept that the ventilatory control system is well organized to prevent upper airway obstructions is discussed.

Afferent pathways for hypoglossal and phrenic responses to changes in upper airway pressure

Our purpose was to determine the afferent pathways underlying reflexes by which changes in upper airway pressure induced alterations in hypoglossal and phrenic nerve activities. An isolated upper airway was produced in decerebrate, vagotomized, paralyzed and ventilated cats. Efferent activities of the phrenic and hypoglossal nerve were monitored. Hypoglossal activity significantly increased following pressure changes in the upper airway of −4 to −21 cm H 2O; phrenic discharge declined in most trials. Similar alterations of neural activities were induced by positive pressures though changes of +14 to +21 cm H 2O were required for significant responses. These changes in hypoglossal and phrenic activities were greatly reduced following bilateral sectionings of hte superior laryngeal nerves but were augmented after the pharyngeal branches of the glossopharyngeal nerves were sectioned. Additional bilateral destruction of the trigeminal nerves almost entirely eliminated response to pressure changes. We conclude tha upper airway receptors may serve to maintain patency of the upper airways. These receptors may play a crucial role in promoting release from upper airway obstructions, especially in sleep.

Receptors responding to changes in upper airway pressure

Our purpose was to characterize receptors which respond to changes in uppr airway pressures. Such changes alterations in hypoglossal and phrenic nerve activities. Decerebrate, vagotomized, paralyzed and ventilated cats were prepared so that pressures could be altered within segments of upper airways. Activities of single fibers in the superior laryngeal and glossopharyngeal nerves were monitored. Most superior laryngeal receptors discharged tonically at zero transmural pressure. Discharges of approximately half decreased (A) and the rest increased (B) with pressure reductions of −7 to −8 cm H 2O. Pressure increases of +7 to +28 cm H 2O caused increases in Group A activities while Group B responses varied. The remaining receptors were silent, being activated by pressure decreases and/or increases. Activities of other silent receptors, similarly activated, were recorded from glossopharyngeal nerve. Tonically active glossopharyngeal receptors increased discharged after both pressure increases and decreases. Most tonically active and silent receptors, having afferents in either nerve, adapted incompletely to sustained pressures. These may have major functions in hypoglossal responses to changes in upper airway pressures.