Discharge patterns of human genioglossus motor units during sleep onset

STUDY OBJECTIVES: Multiunit electromyogram recordings of genioglossus have demonstrated an abrupt reduction in the muscle's activity at sleep onset. Recent evidence from single motor unit recordings indicates that the human genioglossus muscle consists of motor units with a variety of discharge patterns. The aim of the present study was to determine the effect of sleep onset on the activity of individual motor units as a function of their particular discharge pattern. DESIGN: Genioglossus activity was assessed using intramuscular fine-wire electrodes via a percutaneous approach. Sleep onsets (alpha-to-theta transitions) were identified and the genioglossus electromyogram recordings analyzed for single motor unit activity. SETTING: Sleep research laboratory. PARTICIPANTS: Sleep and respiratory data were collected in 8 healthy subjects (6 men). MEASUREMENTS AND RESULTS: One hundred twenty-seven motor units were identified: 23% inspiratory phasic, 45% inspiratory tonic, 4% expiratory phasic, 9% expiratory tonic, 16% tonic, and 3% other. Approximately 50% of inspiratory units (phasic and tonic) ceased activity entirely at sleep onset, whereas those inspiratory units that continued to be active showed a reduction in the proportion of each breath over which they were active. However, the rate of discharge of inspiratory units during the period they did fire was not altered. In contrast, tonic and expiratory units were unaffected by sleep onset, maintaining their discharge pattern over the alpha-to-theta transition. CONCLUSIONS: Central control of inspiratory motoneuron output differs from that of tonic and expiratory units during sleep onset, suggesting that the maintenance of airway patency during sleep may become more reliant on the stiffening properties of tonic and expiratory modulated motor units.     

Motor unit recruitment in human genioglossus muscle in response to hypercapnia

Study Objectives:

Single motor unit recordings of the genioglossus (GG) muscle indicate that GG motor units have a variety of discharge patterns, including units that have higher discharge rates during inspiration (inspiratory phasic and inspiratory tonic), or expiration (expiratory phasic and expiratory tonic), or do not modify their rate with respiration (tonic). Previous studies have shown that an increase in GG muscle activity is a consequence of increased activity in inspiratory units. However, there are differences between studies as to whether this increase is primarily due to recruitment of new motor units (motor unit recruitment) or to increased discharge rate of already active units (rate coding). Sleep-wake state studies in humans have suggested the former, while hypercapnia experiments in rats have suggested the latter. In this study, we investigated the effect of hypercapnia on GG motor unit activity in humans during wakefulness.

Setting:

Sleep research laboratory.

Participants:

Sixteen healthy men.

Measurements and Results:

Each participant was administered at least 6 trials with P_etCO₂ being elevated 8.4 (SD = 1.96) mm Hg over 2 min following a 30-s baseline. Subjects were instrumented for GG EMG and respiratory measurements with 4 fine wire electrodes inserted subcutaneously into the muscle. One hundred forty-one motor units were identified during the baseline: 47% were inspiratory modulated, 29% expiratory modulated, and 24% showed no respiratory related modulation. Sixty-two new units were recruited during hypercapnia. The distribution of recruited units was significantly different from the baseline distribution, with 84% being inspiratory modulated (P < 0.001). Neither units active during baseline, nor new units recruited during hypercapnia, increased their discharge rate as P_etCO₂ increased (P > 0.05 for all comparisons).

Conclusions:

Increased GG muscle activity in humans occurs because of recruitment of previously inactive inspiratory modulated units.

Citation:

Nicholas CL; Bei B; Worsnop C; Malhotra A; Jordan AS; Saboisky JP; Chan JKM; Duckworth E; White DP; Trinder J. Motor unit recruitment in human genioglossus muscle in response to hypercapnia. SLEEP 2010;33(11):1529-1538.     

Discharge Patterns of Human Genioglossus Motor Units during Arousal from Sleep

Study Objectives:

Single motor unit recordings of the human genioglossus muscle reveal motor units with a variety of discharge patterns. Integrated multiunit electromyographic recordings of genioglossus have demonstrated an abrupt increase in the muscle''s activity at arousal from sleep. The aim of the present study was to determine the effect of arousal from sleep on the activity of individual motor units as a function of their particular discharge pattern.

Design:

Genioglossus activity was measured using intramuscular fine-wire electrodes inserted via a percutaneous approach. Arousals from sleep were identified using the ASDA criterion and the genioglossus electromyogram recordings analyzed for single motor unit activity.

Setting:

Sleep research laboratory.

Participants:

Sleep and respiratory data were collected in 8 healthy subjects (6 men).

Measurements and Results:

138 motor units were identified during prearousalarousal sleep: 25% inspiratory phasic, 33% inspiratory tonic, 4% expiratory phasic, 3% expiratory tonic, and 35% tonic. At arousal from sleep inspiratory phasic units significantly increased the proportion of a breath over which they were active, but did not appreciably increase their rate of firing. 80 new units were identified at arousals, 75% were inspiratory, many of which were active for only 1 or 2 breaths. 22% of units active before arousal, particularly expiratory and tonic units, stopped at the arousal.

Conclusions:

Increased genioglossus muscle activity at arousal from sleep is primarily due to recruitment of inspiratory phasic motor units. Further, activity within the genioglossus motoneuron pool is reorganized at arousal as, in addition to recruitment, ∼20% of units active before arousals stopped firing.

Citation:

Wilkinson V; Malhotra A; Nicholas CL; Worsnop C; Jordan AS; Butler JE; Saboisky JP; Gandevia SC; White DP; Trinder J. Discharge patterns of human genioglossus motor units during arousal from sleep. SLEEP 2010;33(3):379-387.     

Electrical stimulation of arterial and central chemosensory afferents at different times in the respiratory cycle of the cat: II. Responses of respiratory muscles and their motor nerves

The response patterns of the electrical activity of the respiratory motor nerves and muscles to brief electrical stimulation of the arterial and the intracranial chemosensory afferents were studied in anesthetized cats. Stimulation during inspiration increased the activity of phrenic nerve and the inspiratory muscles (intercostal, diaphragm) with a latency of 15–25 ms, whereas expiratory muscle activity in the following expiration remained almost unaltered. Stimulation during expiration increased the activity of expiratory nerves and muscles (intercostal, abdominal) after a delay of 80–120 ms. The later the stimulation occurred in the insor expiratory period the larger the increase in amplitude and in steepness of rise of the respective integrated activity in respiratory nerves and muscles. Stimulation in early inspiration shortened the discharge period of inspiratory muscles, whereas excitation in early expiration caused an earlier onset and prolonged the activity in the expiratory muscles. Stimulation in the late phase of ins- or expiration prolonged the discharge of the respective nerves and muscles. Both the arterial (carotid sinus nerve, CSN, and aortic nerve, AN) and intracranial chemosensory (VM) afferents stimuli were able to affect both the inspiratory and the expiratory mechanisms. The restriction of the effects to the phase of the stimulus suggests a mechanism by which these afferents, when activated during inspiration, effectively project only to inspiratory neurones, and vice versa for expiration.Supported by the Deutsche Forschungsgemeinschaft, SFB 114 Bionach     

The output from human inspiratory motoneurone pools

Survival requires adequate pulmonary ventilation which, in turn, depends on adequate contraction of muscles acting on the chest wall in the presence of a patent upper airway. Bulbospinal outputs projecting directly and indirectly to 'obligatory' respiratory motoneurone pools generate the required muscle contractions. Recent studies of the phasic inspiratory output of populations of single motor units to five muscles acting on the chest wall (including the diaphragm) reveal that the time of onset, the progressive recruitment, and the amount of motoneuronal drive (expressed as firing frequency) differ among the muscles. Tonic firing with an inspiratory modulation of firing rate is common in low intercostal spaces of the parasternal and external intercostal muscles but rare in the diaphragm. A new time and frequency plot has been developed to depict the behaviour of the motoneurone populations. The magnitude of inspiratory firing of motor unit populations is linearly correlated to the mechanical advantage of the intercostal muscle region at which the motor unit activity is recorded. This represents a 'neuromechanical' principle by which the CNS controls motoneuronal output according to mechanical advantage, presumably in addition to the Henneman's size principle of motoneurone recruitment. Studies of the genioglossus, an obligatory upper airway muscle that helps maintain airway patency, reveal that it receives simultaneous inspiratory, expiratory and tonic drives even during quiet breathing. There is much to be learned about the neural drive to pools of human inspiratory and expiratory muscles, not only during respiratory tasks but also in automatic and volitional tasks, and in diseases that alter the required drive.     

Distribution of inspiratory drive to the external intercostal muscles in humans

The external intercostal muscles in humans show marked regional differences in respiratory effect, and this implies that their action on the lung during breathing is primarily determined by the spatial distribution of neural drive among them. To assess this distribution, monopolar electrodes were implanted under ultrasound guidance in different muscle areas in six healthy individuals and electromyographic recordings were made during resting breathing. The muscles in the dorsal portion of the third and fifth interspace showed phasic inspiratory activity with each breath in every subject. However, the muscle in the ventral portion of the third interspace showed inspiratory activity in only three subjects, and the muscle in the dorsal portion of the seventh interspace was almost invariably silent. Also, activity in the ventral portion of the third interspace, when present, and activity in the dorsal portion of the fifth interspace were delayed relative to the onset of activity in the dorsal portion of the third interspace. In addition, the discharge frequency of the motor units identified in the dorsal portion of the third interspace averaged (mean ± s.e.m .) 11.9 ± 0.3 Hz and was significantly greater than the discharge frequency of the motor units in both the ventral portion of the third interspace (6.0 ± 0.5 Hz) and the dorsal portion of the fifth interspace (6.7 ± 0.4 Hz). The muscle in the dorsal portion of the third interspace started firing simultaneously with the parasternal intercostal in the same interspace, and the discharge frequency of its motor units was even significantly greater (11.4 ± 0.3 vs. 8.9 ± 0.2 Hz). These observations indicate that the distribution of neural inspiratory drive to the external intercostals in humans takes place along dorsoventral and rostrocaudal gradients and mirrors the spatial distribution of inspiratory mechanical advantage.     

Reorganisation of respiratory network activity after loss of glycinergic inhibition

gamma-Aminobutyric acid (GABA)-ergic and glycinergic inhibition is believed to play a major role in the respiratory network. In the present study we tested whether specific blockade of glycinergic inhibition resulted in changes in respiratory network interaction and function. Using the working heart-brainstem preparation from adult mice, we recorded phrenic nerve activity and the activity of different types of respiratory neurones located in the ventrolateral medulla. Strychnine (0.03-0.3 microM) was given systemically to block glycine receptors (Gly-R). During exposure to strychnine, post-inspiratory (PI) neurones shifted their onset of discharge into the inspiratory phase. As a consequence, the post-inspiratory phase failed and the rhythm changed from a three-phase cycle (inspiration, post-inspiration, expiration, with a frequency of about. 0.24 Hz) to a faster, two-phased cycle (inspiration expiration, frequency about 0.41 Hz). Inspiratory and expiratory neurones altered their augmenting membrane potential pattern to a rapidly peaking pattern. Smaller voltage oscillations at approximately 10 Hz and consisting of excitatory and inhibitory postsynaptic potential sequences occurred during the expiratory interval. Due to their high frequency and low amplitude, such oscillations would be inadequate for lung ventilation. We conclude that, under physiological conditions, glycinergic inhibition does indeed play a major role in the generation of a normal respiratory rhythm in adult mice. After failure of glycinergic inhibition a faster respiratory rhythm seems to operate through reciprocal GABAergic inhibition between inspiratory and expiratory neurones, while phase switching is organised by activation of intrinsic membrane properties.     

Effects of Auditory Stimulation on Respiration

Each of 40 college students received 6 presentations of white noise at an intensity of either SO or 110 dB during either inspiration or expiration. Changes in tidal volume, inspiratory period, and expiratory period elicited by that stimulation were studied. Auditory stimulation produced respiratory changes which could be regarded conveniently as two phasic responses. We labeled these responses the initial phasic response and the delayed phasic response. The initial response was limited to the respiratory period during which stimulation was delivered, it consisted of a brief inspiratory movement which increased the speed of inspiratory periods during which it occurred but decreased the speed of expiratory periods during which it occurred. In either case, the initial phasic response increased ventilation. The delayed phasic response was an increase both in speed and tidal volume of respiratory cycles subsequent to the period during which stimulation was delivered. Like the initial response, the delayed response increased ventilation. The effects of the delayed response were more widespread when stimulation was delivered during expiration rather than during inspiration. Stimulus intensity and stimulus repetition respectively potentiated and attenuated both the initial and the delayed phasic response. The findings are compared with those of earlier research on respiratory changes elicited by auditory stimulation.     

Possible involvement of the facial nucleus in regulation of respiration in rats

The facial nucleus (FN) has been known as a motor nucleus to control the activity of the facial skeletal muscles by its efferent somatic motoneurons. Much less, however, is known about the non-motor control functions of its interneurons. The present study was designed to investigate if the interneurons of the FN participate in controlling rhythmic respiration in the sodium thiopental-anesthetized and vagotomized Sprague-Dawley rats with facial motoneurons retrogradely degenerated with techniques of electrical and chemical stimulation of the FN and extracellular recording of discharge of neurons in the FN. Single pulse stimulation (75-100 microA, 0.2 ms) of the FN during inspiration caused a transient restrain in phrenic discharge. Short train stimulation (75-100 microA, 0.2 ms, 100 Hz, 3-5 pulses) delivered during the early- or mid-term of inspiration augmented the inspiratory duration, but switched the inspiration off when delivered during the later stage of inspiration. Short train stimulation delivered during expiration prolonged the expiratory duration. Continuous stimulation could inhibit the inspiration. Microinjection of kainic acid into the FN caused an augmentation in inspiratory duration and amplitude and in expiratory duration. These data indicate that the interneurons of the FN might participate in the modulation of respiration. Different discharge patterns of interneurons in the FN, interestingly some respiratory related patterns, were observed, which provide a possible structural basis for the role of the FN in respiratory regulation.     

Tonic and phasic drive to medullary respiratory neurons during periodic breathing

It is unknown how central neural activity produces the repetitive termination and restart of periodic breathing (PB). We hypothesized that inspiratory and expiratory neural activities would be greatest during the waxing phase and least during the waning phase. We analyzed diaphragmatic and medullary respiratory neural activities during PB in intact unanesthetized adult cats. Diaphragmatic activity was increased and phasic during the waxing phase and was decreased and tonic during the waning phase. Activity of expiratory (n=21) and inspiratory (n=40) neurons was generally increased and phasic during the waxing phase and was decreased and more tonic during the waning phase. During apneas associated with PB, diaphragmatic activity was silent and most, but not all, inspiratory cells were inactive whereas most expiratory cells decreased activity but remained tonically active. We suggest that reduced strength of reciprocal inhibition, secondary to reduced respiratory drive, allows for simultaneous tonic activity of inspiratory and expiratory neurons of the central pattern generator, ultimately resulting in central apnea.     

Upper airway function during sleep and wakefulness: experimental studies on normal and anesthetized cats.

Normal (N = 6) and anesthetized (N = 70) cats were used to study the laryngeal abductors, the posterior cricoarytenoid (PCA) muscles, during sleep and wakefulness and to investigate sites within the brainstem that influenced PCA and diaphragmatic activity. The findings were as follows: 1. During wakefulness, PCA activity occurred throughout the respiratory cycle but was most intense during inspiration. Both expiratory and inspiratory PCA activity declined during sleep--the former more so than the latter. The decline in abductor activity was maximal in REM sleep. 2. Barbiturate anesthesia, according to the dosage, produced PCA activity patterns characteristic of either wakefulness or sleep. 3. The brainstem between A4 and P14 was mapped with stimulating electrodes. Rostral brainstem sites showed predominantly facilitatory effects of PCA activity; caudal sites produced predominantly blocking effects. 4. PCA facilitation consisted of (a) an increase in the duration of the PCA burst, (b) and increase in the discharge frequency of the PCA motor units, and (c) a recruitment of larger motor units. PCA blocking effects were the opposite, i.e., burst durations were shortened and motor units were decruited. 5. Facilitatory sites produced clear change in intensity and duration of PCA activity at stimulation intensities below those necessary to obtain changes in the intensity of diaphragmatic activity. 6. Stimulation of facilitatory sites during expiration caused phase switching to inspiration. In some cases, stimulation during inspiration caused phase switching to expiration. The results are discussed in terms of their implications for the obstructive apneas of sleep and in terms of the neural control of breathing.     

Serotonin and cervical respiratory motoneurones: intracellular study in the newborn rat brainstem-spinal cord preparation

Summary Previous experiments performed in the in vitro newborn rat brainstem-spinal cord preparation reported that the addition of serotonin (5-HT, 30–50 M) to the bathing medium induced increases in the respiratory frequency and a large tonic discharge on all the cervical ventral roots. The aim of the present work was to define whether the 5-HT-induced tonic discharge involved respiratory or non-respiratory motoneurones. Intracellular recordings demonstrated that cervical (C2) motoneurones (n = 27) were depolarized by 5-HT but that the 5-HT-induced tonic discharge was mainly due to recruitment of silent motoneurones (n = 18) which fired permanently (15/18; 17 ±3 Hz) under 5-HT. The respiratory motoneurones (n = 9) retained a phasic inspiratory discharge (5/9), even if some (4/9) occasionally exhibited a few spikes during expiration. Therefore, it is concluded that the 5-HT-induced tonic discharge is unlikely to have functional significance in respiration.     

Studies of the pulmonary vagal control of central respiratory rhythm in the absence of breathing movements

1. Breuer's hypothesis that the vagus nerves exert a tonic control of respiratory rhythm, in addition to the phasic control, was examined.2. Closed-chest cardiopulmonary bypass was instituted in dogs weighing 20-30 kg anaesthetized with chloralose. Respiratory rhythm was recorded from a phrenic electroneurogram.3. Complete muscular paralysis induced with gallamine triethiodide produced an increase in the duration of inspiration and an increase in the amplitude of the integrated phrenic electroneurogram. There was no consistent effect on expiratory duration. Gallamine produced no effect when given after vagotomy.4. In the paralysed state, an increase in lung volume of 25-100 ml. for 30-60 sec produced a sustained increase in the duration of expiration and a decrease of respiratory rate: there was little effect on inspiratory duration, or the amplitude of the integrated phrenic electroneurogram.5. A decrease in lung volume of the same order of magnitude for the same period produced a sustained decrease in the duration of expiration and an increase of respiratory rate: there was little effect on inspiratory duration or the amplitude of the integrated phrenic electroneurogram.6. The phenomena described in (5) and (6) constitute a high gain respiratory frequency controller. They did not occur after bilateral cervical vagotomy.7. Bilateral cervical vagotomy during complete muscular paralysis produced a further increase in the duration of inspiration and in the amplitude of the integrated phrenic electroneurogram; there was no consistent effect on expiratory duration.8. The results confirmed Breuer's hypothesis and showed that inspiratory duration and expiratory duration are controlled independently.     

Activity of Brainstem Respiratory Neurones just before the Expiration-Inspiration Transition in the Rat

Inspiratory activity of the hypoglossal nerve (XIIn) often precedes that of the phrenic nerve (PHRn). By manipulating artificial respiration, this preceding activity (pre-I XIIn activity) can be lengthened or isolated prematurely (decoupled XIIn activity) without developing into overt PHRn-associated inspiratory bursts. We hypothesized that these pre-I and decoupled XIIn activities, collectively termed 'XIIn-w/o-PHRn activity', reflect certain internal states of the respiratory centre at the period just prior to the transition from the expiratory phase to the inspiratory phase. In decerebrate, neuromuscularly blocked and artificially ventilated rats, the firing properties of medullary respiratory neurones were examined during the period of the XIIn-w/o-PHRn activity. The majority of the inspiratory neurones examined could be classified into two types: one was active (XIIn-type) and the other was inactive (PHRn-type) during the XIIn-w/o-PHRn period. On the other hand, augmenting expiratory (E-AUG) neurones of the Bötzinger complex (BOT) and the caudal ventral respiratory group (VRG) fired intensively during this period. Their firing stopped at the onset of the overt inspiratory bursts in the XIIn and PHRn, suggesting that BOT E-AUG neurones inhibit PHRn-type, but not XIIn-type, inspiratory neurones. We hypothesize that XIIn-type inspiratory activity facilitates the phase change from expiration to inspiration, through activation of certain inspiratory neurones that inhibit the firing of BOT E-AUG neurones and generation of the overt inspiratory bursts in XIIn-type and PHRn-type inspiratory neurones.     

Function of scalene muscles under conditions of quiet breathing and inspiratory resistive load

Low-threshold slow motor units in feline scalene muscle generated spontaneous discharges (6–8 imp/sec) during resting ventilation, which were independent of the respiration cycle. Under conditions of resistive load, activity of these motor units and its electromyographic pattern changed from tonic towards phasic type, synchronized with the inspiration phase. Removal of the load restored the initial pattern of activity. Clear dependency of activity transformations on respiratory load implies a functional modulation of respiratory neural drive to the scalene muscles and the role of these muscles in compensation of inspiratory load. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 12, pp. 623–626, December 1999     

Medullary respiratory neural activity during hypoxia in NREM and REM sleep in the cat

Intact unanesthetized cats hyperventilate in response to hypocapnic hypoxia in both wakefulness and sleep. This hyperventilation is caused by increases in diaphragmatic activity during inspiration and expiration. In this study, we recorded 120 medullary respiratory neurons during sleep in hypoxia. Our goal was to understand how these neurons change their activity to increase breathing efforts and frequency in response to hypoxia. We found that the response of medullary respiratory neurons to hypoxia was variable. While the activity of a small majority of inspiratory (58%) and expiratory (56%) neurons was increased in response to hypoxia, the activity of a small majority of preinspiratory (57%) neurons was decreased. Cells that were more active in hypoxia had discharge rates that averaged 183% (inspiratory decrementing), 154% (inspiratory augmenting), 155% (inspiratory), 230% (expiratory decrementing), 191% (expiratory augmenting), and 136% (expiratory) of the rates in normoxia. The response to hypoxia was similar in non-rapid-eye-movement (NREM) and REM sleep. Additionally, changes in the profile of activity were observed in all cell types examined. These changes included advanced, prolonged, and abbreviated patterns of activity in response to hypoxia; for example, some inspiratory neurons prolonged their discharge into expiration during the postinspiratory period in hypoxia but not in normoxia. Although changes in activity of the inspiratory neurons could account for the increased breathing efforts and activity of the diaphragm observed during hypoxia, the mechanisms responsible for the change in respiratory rate were not revealed by our data.     

The activity of respiratory neurons before and during panting in the cat

The effects of heating the preoptic/anterior hypothalamic (PO/AH) region on medullary respiratory neurons were studied in urethane-anesthetized, spontaneously breathing cats. The efferent phrenic nerve discharge or the pneumotachogram served as an indicator of central respiratory periodicity. In each animal, heating of the PO/AH area caused panting, defined as an increase of respiratory rate over 100 breaths per minute. During polypnea similar changes in the discharge patterns of both inspiratory and expiratory neurons were observed. There was a significant decrease in the duration of the discharge phase and the number of impulses per burst so that a reciprocal relationship existed between these parameters and respiratory rate. However, the average impulse frequency within a burst was higher during panting and could be shown to be a linear function of respiratory rate. Due to the concomitant decrease in inspiration and expiration times, the average discharge frequency per cycle time also increased in both inspiratory and expiratory medullary neurons. For continuously discharging neurons which displayed a higher frequency during the inspiration period (frequency modulated discharge), the phasic linkage remained unchanged during polypneic panting. From our results it is concluded that local heating of the PO/AH region shifts the entire respiratory system to a higher level of activity which can be correlated with ventilatory changes during panting.     

Respiratory interneurons of the lower cervical (C4-C5) cord: membrane potential changes during fictive coughing,vomiting, and swallowing in the decerebrate cat

The possible roles of interneurons in the C4-C5 cervical spinal cord in conveying central drives to phrenic motoneurons during different behaviour patterns were investigated using intracellular recordings in decerebrate, paralysed, artificially ventilated cats. Eleven cells were tentatively classified as respiratory interneurons since they: (i) could not be antidromically activated from the ipsilateral whole intrathoracic phrenic nerve, and (ii) exhibited large membrane potential changes during eupnea (7.3 mV±3.6, range 2–13.5 mV) or non-respiratory behaviour patterns. Six neurons depolarized in phase with phrenic discharge; four others depolarized during the expiratory phase; one neuron exhibited depolarization during the end of both expiration and inspiration. A variety of responses was observed during fictive coughing, vomiting, and swallowing. The results are consistent with C4-C5 expiratory interneurons conveying inhibition to phrenic motoneurons during different behaviour patterns. The responses of inspiratory and multiphasic neurons suggest that the roles of these interneurons are mode complex than simply relaying central excitatory or inhibitory drive to phrenic motoneurons.     

Modulation of expiratory motor output evoked by chemical activation of pre-Bötzinger complex in vivo

We have previously demonstrated that chemical stimulation of the pre-B?tzinger complex (pre-B?tC) in the anesthetized cat produces either phasic or tonic excitation of phrenic nerve discharge. This region is characterized by a mixture of inspiratory-modulated, expiratory-modulated, and phase-spanning (including pre-inspiratory (pre-I)) neurons; however, its influence on expiratory motor output is unknown. We, therefore, examined the effects of chemical stimulation of the pre-B?tC on expiratory motor output recorded from the caudal iliohypogastric (lumbar, L(2)) nerve. We found that unilateral microinjection of DL-homocysteic acid (DLH; 10 mM; 10-20 nl) into 16 sites in the pre-B?tC enhanced lumbar nerve discharge, including changes in timing and patterning similar to those previously reported for phrenic motor output. Both increased peak amplitude and frequency of phasic lumbar bursts as well as tonic excitation of lumbar motor activity were observed. In some cases, evoked phasic lumbar nerve activity was synchronized in phase with phrenic nerve discharge. These findings demonstrate that chemical stimulation of the pre-B?tC not only excites inspiratory motor activity but also excites expiratory motor output, suggesting a role for the pre-B?tC in generation and modulation of inspiratory and expiratory rhythm and pattern.     

The importance of timing on the respiratory effects of intermittent carotid sinus nerve stimulation

1. The respiratory response, measured directly as tidal volume or indirectly by using integrated peak phrenic activity, to intermittent electrical stimulation of the carotid sinus nerve was determined in anaesthetized cats.2. Stimulation at rates of 20-25 Hz for 0.5 sec had a rapid effect, increasing inspiratory airflow and phrenic discharge, but only if applied during inspiration. An increase in tidal volume or peak level of integrated phrenic discharge occurred only if the stimulus was exhibited during the second half of inspiration. Continuous stimulation had no greater effect on size or frequency of breathing than did intermittent inspiratory stimuli alone. Stimulation during expiration had no effect on the form or magnitude of subsequent breaths.3. Stimuli in expiration led to a prolongation of expiration. Stimuli in late inspiration caused a prolongation of both inspiration and expiration. Because of these effects, the respiratory rate could be changed by stimulation; in some instances entrainment of respiration by the intermittent carotid sinus nerve stimuli occurred.4. The findings are attributable to modulation of incoming carotid sinus nerve information by the central respiratory neurones, which use primarily that which arrives during inspiration. They show a possible mechanism by which oscillating signals may have a different effect than their mean level would indicate.