Extra-segmental reflexes derived from intercostal afferents: phrenic and laryngeal responses

1. Phrenic and recurrent laryngeal efferent responses were evoked by brief tetani or single shocks to the cut external intercostal nerves of anaesthetized cats. The reflexes derived from middle thoracic segments (T5 and 6) were compared with those emanating from caudal thoracic segments (T9 and 10).2. During inspiration, middle intercostal nerve stimulation transiently inhibited the spontaneous discharge in both efferent neurograms, whereas stimulation of caudal intercostal nerves facilitated phrenic discharge and usually inhibited recurrent laryngeal activity.3. During expiration, stimulation at either thoracic level enhanced recurrent laryngeal discharge while provoking little or no phrenic response.4. Superficial lesions of the lateral cervical cord, ipsilateral to the stimulus sites, above or below the phrenic outflow, eliminated all reflex responses except the phrenic response to caudal thoracic stimuli. Similarly, in the spinal animal, middle intercostal afferents could not be shown to decrease phrenic excitability. Caudal intercostal afferents cause phrenic excitation by a spinal reflex.5. Group I afferents of the mid-thoracic segments and group II afferents of the caudal thoracic segments initiate these extra-segmental reflexes.6. The recurrent laryngeal responses manifest, for the most part, changes in the discharge of fibres innervating the posterior cricoarytenoid muscle. The responses fit the overall pattern of response to middle intercostal nerve stimulation, namely, inhibition of inspiratory muscles and excitation of expiratory muscles. Intercostal afferent stimulation also activated the laryngeal adductor muscles.7. The results support the view that intercostal mechanoreceptors initiate an array of extra-segmental respiratory reflexes, including spinal and supraspinal arcs. The simplest way to account for the various responses to stimulation of middle intercostal afferents is to postulate a reflex involving supraspinal respiratory neurones.8. The observed reflexogenic differences correlate with anatomical differences between the middle and caudal ribs. Possible functional implications of this relationship are discussed.     

Activation of respiratory afferents by resistive loaded breathing modifies somatosensory evoked potentials to median nerve stimulation in humans

The cortical projections of respiratory afferents (vagus and respiratory muscle nerves) are well documented in humans. It is also shown that their activation during loaded breathing modifies the perception of tactile sensation as well as the motor drive to skeletal muscles. The effects of expiratory or inspiratory loaded breathing on somatosensory evoked potentials (SEPs) elicited by median nerve stimulation were studied in eight healthy subjects. No significant changes occurred in latencies of N20, N30 and P40 throughout the expiratory loading period, except for a significant lengthening in P1 latency compared with unloaded breathing. However, inspiratory loading induced a significant increase in peak latency of N20, N30 and P40 components. We suggest that projections of inspiratory afferents from the diaphragm and the intercostal muscles, activated by inspiratory loading, could be responsible for the lengthened latency of median nerve SEP components. Thus, respiratory afferents very likely interact with pathways of the somatosensory system.     

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.     

Patterns of spontaneous and reflexly-induced activity in phrenic and intercostal motoneurons

Summary The discharge frequencies of 35 single phrenic and 13 inspiratory intercostal motoneurons were recorded in anaesthetised paralysed cats. Chemical stimulation by asphyxia or hypercapnia increased the discharge frequency and number of motoneurons active within each inspiratory discharge without altering the general pattern of respiratory activity, but mechanical stimulation of the epipharynx and electrical stimulation of the pharyngeal branch of the glossopharyngeal nerve caused repetitive bursts of very high frequency (up to 400 impulses/ sec) in inspiratory motoneurons, with disruption of their normal phasic activity. The latency of the motoneuron response to electrical stimulation of the glossopharyngeal nerve ranged from 15–30 msec and varied with respiratory phase, being shorter during spontaneous inspiratory activity.Phrenic motoneurons were divided according to their order of recruitment during inspiratory activity, and the later recruited (high-threshold) units had significantly larger spike amplitudes than motoneurons which discharged throughout inspiration. High-threshold motoneurons also achieved higher maximum discharge frequencies in response to electrical stimulation of the glossopharyngeal nerve, and it is suggested that these properties are important in increasing the tension developed by respiratory muscles near the end of inspiration when there is greater elastic resistance to lung inflation.     

Responses of ventral respiratory neurones in the rat to vagus stimulation and the functional division of expiration.

In anaesthetized rats, extracellular and intracellular recordings were taken from 106 respiratory neurones in the intermediate region of the nucleus ambiguus. We observed unprovoked shortening of expiratory time accompanied, in all classes of respiratory neurone, by the elimination of the changes in membrane potential that were characteristic of stage II expiration. The demonstration of the elimination of stage II expiration in both the rat and cat strongly supports the functional division of expiration into stage I expiration (post-inspiration) and stage II expiration. In order to identify the neurones in the rat that receive inputs from vagal afferents and modulate the central respiratory rhythm, we examined whether any respiratory neurones responded to stimulation of the vagus nerve. Some post-inspiratory and stage II expiratory neurones responded. The short latency (< 2 ms) of four of the responses indicates that some vagal afferents act on post-inspiratory neurones via a disynaptic pathway. While repetitive stimulation of the vagus nerve could inhibit the phrenic rhythm, it appears that most inspiratory neurones in the intermediate region of the nucleus ambiguous complex are not directly involved in integrating the information from vagal afferents with the central respiratory rhythm.     

Synaptic effects of intercostal tendon organs on membrane potentials of medullary respiratory neurons

1. Stimulation of intercostal muscle tendon organs or their afferent fibers reduces medullary inspiratory neuron activity, decreases motor output to inspiratory muscles, and increases the activity of expiratory laryngeal motoneurons. The present study examines the synaptic mechanisms underlying these changes to obtain information about medullary neurons that participate in the afferent limb of this reflex pathway. 2. Membrane potentials of medullary respiratory neurons were recorded in decerebrate paralyzed cats. Postsynaptic potentials (PSPs) elicited in these neurons by intercostal nerve stimulation (INS) were compared before and after intracellular iontophoresis of chloride ions. After chloride injection, the normal hyperpolarization caused by inhibitory (I) PSPs is "reversed" to depolarization. 3. In inspiratory neurons, reversal of IPSPs by chloride injection also reversed hyperpolarization produced by INS when applied during any portion of the respiratory cycle. This observation suggests that increased chloride conductance of the postsynaptic membrane mediated the inhibition. Further, it is very likely that the last-order interneuron in the afferent pathway must be excited by INS and alter inspiratory neuron activity via an inhibitory synapse. The linear relationship between the amplitude of the INS induced PSP and membrane potential of inspiratory neurons provided evidence that neurons in the afferent pathway are not respiratory modulated. 4. The membranes of expiratory vagal motoneurons and post-inspiratory neurons were depolarized by INS during all portions of the respiratory cycle before IPSP reversal. Reversal of IPSPs affected neither this depolarization of expiratory vagal motoneurons during stage I and II expiration nor that of post-inspiratory neurons during stage I expiration. Thus this depolarization probably resulted from synaptic excitation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory modulation of the cutaneous somatosympathetic reflex in normotensive (WKY) and in spontaneously hypertensive rats (SHR): species and strain-dependent patterns

In 6 normotensive Wistar-Kyoto (WKY) and 6 spontaneously hypertensive rats (SHRs) anesthetized with urethane and chloralose, paralyzed, artificially ventilated, vagotomized with carotid sinus nerves bilaterally cut, somatosympathetic reflex discharges were recorded in cervical and renal nerves by stimulating group II and III cutaneous afferents in the sural nerve. Only a long-circuited, late supraspinal component reflex discharge could be elicited. After averaging the responses evoked by random stimulation, the latency of the reflex discharge was significantly longer in the renal than in the cervical sympathetic nerve, equally in the WKY rat and in SHR. In WKY rats the peak of sympathetic discharge corresponded to early expiration, whereas in SHRs--to late inspiratory phase. The duration of the reflex discharge elicited in inspiration was greater in SHR than in WKY rats. In WKY rats stimuli applied during phrenic discharge produced a reflex response of longer latency and of reduced amplitude than those applied in expiration. In SHRs the latency of the reflex response in the sympathetic cervical nerve was shorter during inspiration than in expiratory phase. The timing of the sympathetic reflex responsiveness within respiratory cycle in SHR and in WKY rats corresponded to strain-dependent opposite respiratory synchronization pattern of the spontaneous sympathetic activity characterizing each strain. No respiratory modulation of the somatosympathetic reflex was observed in the renal nerve of SHR. It is concluded that both spontaneous and evoked sympathetic activity is synchronized differently in SHR and in WKY rats and this difference is both species- and strain-dependent.     

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.     

Expiratory activity of the inspiratory muscles during cough.

To investigate the neural mechanism of the expiratory activity of the inspiratory muscles during a cough, EMG of the respiratory muscles were recorded in anesthetized and tracheostomized dogs. A laparoscope was used to minimize injury to the abdominal muscles for implantation of the electrodes into the costal diaphragm. During the expulsive phase of a cough, the diaphragm was active in 7 of 12 dogs and the external intercostal muscle was active in 3 of 6 dogs. During a cough, the expiratory activity of the diaphragm, after the termination of its inspiratory activity, started at 52.9 +/- 24.6 ms, and that of external intercostal muscle started at 51.1 +/- 20.5 ms. The expiratory activity of the internal intercostal muscle and of the transversus abdominis started at 34.3 +/- 13.0 and 27.8 +/- 15.2 ms, respectively. The onset of expiratory activity of the inspiratory muscles is significantly later than that of expiratory muscles. Continuous activity in the expiratory muscles evoked by airway occlusion, i.e., Hering-Breuer reflex, was suppressed during the inspiratory phase of a cough, but not suppressed during the expulsive phase even when the expiratory activity of the diaphragm was observed. We concluded that the expiratory activity of inspiratory muscles is controlled independently of both expiratory activity of the expiratory muscles and inspiratory activity of the inspiratory muscles.     

Electrical stimulation of arterial and central chemosensory afferents at different times in the respiratory cycle of the cat: I. Ventilatory responses

Ventilatory responses to stimulation of chemoreceptor afferents were studied in the anesthetized, spontaneously breathing cat. Short bursts of electrical stimuli were applied, at various times in the inspiratory or expiratory phase of consecutive breaths, to the carotid sinus (CSN) and aortic nerves (AN) and to the ventral medulla (VM), and effects on tidal volume (V _T), inspiratory, expiratory and cycle durationst _I,t _E,t _tot) and in ventilation (_E) were measured. The responses evoked by stimulating CSN, AN and VM were qualitatively the same, although there were quantitative differences. It was found that effects of stimulation in expiration were restricted to the expiratory phase, and vice versa for inspiration. Stimulation during both inspiration and expiration resulted in increasedV _T, by increasing end-inspiratory or decreasing end-expiratory lung volume, respectively, and also increased ventilation, _E. These effects were most marked in response to stimulation in inspiration. During both phases there was an increasing effect with increasing delay of the stimulus,t _St, from onset of inspiration or expiration, respectively. There was a continuous increase int _I, from below control to above control values, with increasingt _St during inspiration and similarly fort _E during expiration. Hence, the total respiratory cycle duration was shortened when a stimulus was applied early in either phase, and was prolonged, when it was applied late. The results show that stimulation of peripheral and of central chemoafferents exerts qualitatively similar effects on respiration. The central neuronal mechanisms generating both inspiration and expiration show the same changes in reactivity in the respiratory cycle.Supported by the Deutsche Forschungsgemeinschaft, SFB 114 Bionach     

Effect of stimulation of the medial and lateral zones of the respiratory center on electrical activity of the diaphragm,intercostal muscles,and phrenic neurons

Experiments on cats showed that the nucleus of the tractus solitarius contains zones during stimulation of which electrical activity of the phrenic neurons and diaphragm is selectively stimulated or inhibited. Stimulation of inspiratory and expiratory zones of the nucleus ambiguus influences the electrical activity of the external intercostal muscles. During stimulation of the corresponding zones in the gigantocellular nucleus electrical activity is changed in both groups of inspiratory muscles simultaneously. It is postulated that the action of stimulation of the zones of the gigantocellular nucleus on both groups of inspiratory muscles is indirect in its mechanism, through neurons of the nucleus of the tractus solitarius and nucleus ambiguus.Academy of Medical Sciences of the USSR Group, Kuibyshev Medical Institute. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 4, pp. 392–395, April, 1978.     

Reflex prolongation of stage I of expiration

Experiments were performed on anesthetized cats to test the theory that the interval between phrenic bursts is comprised of two phases, stage I and stage II of expiration. Evidence that these represent two separate neural phases of the central respiratory rhythm was provided by the extent to which stage duration is controlled individually when tested by superior laryngeal, vagus and carotid sinus nerve stimulation. Membrane potential trajectories of bulbar postinspiratory neurons were used to identify the timing of respiratory phases.Stimulation of the superior laryngeal, vagus and carotid sinus nerves during stage I of expiration prolonged the period of depolarization in postinspiratory neurons without significantly changing the durations of either stage II expiratory or inspiratory inhibition, indicating a fairly selective prolongation of the first stage of expiration. Changes in subglottic pressure, insufflation of smoke into the upper airway, application of water to the larynx or rapid inflation of the lungs produced similar effects. Sustained tetanic stimulation of superior laryngeal and vagus nerves arrested the respiratory rhythm in stage I of expiration. Membrane potentials in postinspiratory, inspiratory and expiratory neurons were indicative of a prolonged postinspiratory period. Thus, such an arrhythmia can be described as a postinspiratory apneic state of the central oscillator. The effects of carotid sinus nerve stimulation reversed when the stimulus was applied during stage II expiration. This was accompanied by corresponding changes in the membrane potential trajectories in postinspiratory neurons.The results manifest a ternary central respiratory cycle with two individually controlled phases occurring between inspiratory bursts.     

Role of the ventrolateral region of the nucleus of the tractus solitarius in processing respiratory afferent input from vagus and superior laryngeal nerves

Summary The role of respiratory neurons located within and adjacent to the region of the ventrolateral nucleus of the tractus solitarius (vlNTS) in processing respiratory related afferent input from the vagus and superior laryngeal nerves was examined. Responses in phrenic neural discharge to electrical stimulation of the cervical vagus or superior laryngeal nerve afferents were determined before and after lesioning the vlNTS region. Studies were conducted on anesthetized, vagotomized, paralyzed and artificially ventilated cats. Arrays of 2 to 4 tungsten microelectrodes were used to record neuronal activity and for lesioning. Constant current lesions were made in the vlNTS region where respiratory neuronal discharges were recorded. The region of the vlNTS was probed with the microelectrodes and lesions made until no further respiratory related neuronal discharge could be recorded. The size and placement of lesions was determined in subsequent microscopic examination of 50 m thick sections. Prior to making lesions, electrical stimulation of the superior laryngeal nerve (4–100 A, 10 Hz, 0.1 ms pulse duration) elicited a short latency increase in discharge of phrenic motoneurons, primarily contralateral to the stimulated nerve. This was followed by a bilateral decrease in phrenic nerve discharge and, at higher currents, a longer latency increase in discharge. Stimulation of the vagus nerve at intensities chosen to selectively activate pulmonary stretch receptor afferent fibers produced a stimulus (current) dependent shortening of inspiratory duration. Responses were compared between measurements made immediately before and immediately after each lesion so that changes in response efficacy due to lesions per se could be distinguished from other factors, such as slight changes in the level of anesthesia over the several hours necessary in some cases to complete the lesions. Neither uni- nor bi-lateral lesions altered the efficacy with which stimulation of the vagus nerve shortened inspiratory duration. The short latency excitation of the phrenic motoneurons due to stimulation of the superior laryngeal nerve was severely attenuated by unilateral lesions of the vlNTS region ipsilateral to the stimulated nerve. Neither the bilateral inhibition nor the longer latency excitation due to superior laryngeal nerve stimulation was reduced by uni- or bi-lateral lesions of the vlNTS region. These results demonstrate that extensive destruction of the region of the vlNTS: a) does not markedly affect the inspiratory terminating reflex associated with electrical stimulation of the vagus nerve in a current range selective for activation of pulmonary stretch receptor afferents, and b) abolishes the short-latency increase, but not the bilateral decrease or longer latency increase in phrenic motoneuronal discharge which follows stimulation of the superior laryngeal nerve. We conclude that respiratory neurons in the region of the vlNTS do not play an obligatory role in the respiratory phase transitions in this experimental preparation. Neurons in the vlNTS region may participate in other reflexes, such as the generation of augmented phrenic motoneuronal discharge in response to activation of certain superior laryngeal or vagus nerve afferents.     

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.     

Tonic and phasic respiratory drives to human genioglossus motoneurons during breathing

A tongue muscle, the genioglossus (GG), is important in maintaining pharyngeal airway patency. Previous recordings of multiunit electromyogram (EMG) suggest it is activated during inspiration in humans with some tonic activity in expiration. We recorded from populations of single motor units in GG in seven subjects during quiet breathing when awake. Ultrasonography assisted electrode placement. The activity of single units was separated into six classes based on a step-wise analysis of the discharge pattern. Phasic and tonic activities were analyzed statistically with the coefficient of determination (r2) between discharge frequency and lung volume. Of the 110 motor units, 29% discharged tonically without phasic respiratory modulation (firing rate approximately 19 Hz). Further, 16% of units increased their discharge during expiration (expiratory phasic and expiratory tonic units). Only half the units increased their discharge during inspiration (inspiratory phasic and inspiratory tonic units). Units firing tonically with an inspiratory increase had significantly higher discharge rates than those units that only fired phasically (peak rates 25 vs. 16 Hz, respectively). Simultaneous recordings of two or three motor units showed neighboring units with differing respiratory and tonic drives. Our results provide a classification and the first quantitative measures of human GG motor-unit behavior and suggest this activity results from a complex interaction of inspiratory, expiratory, and tonic drives at the hypoglossal motor nucleus. The presence of different drives to GG implies that complex premotor networks can differentially engage human hypoglossal motoneurons during respiration. This is unlike the ordered recruitment of motor units in limb and axial muscles.     

The importance of timing on the respiratory effects of intermittent carotid body chemoreceptor stimulation

1. The respiratory response, measured directly as tidal volume or indirectly by using integrated peak phrenic activity, to brief intermittent chemical stimulation or depression of the carotid body was determined in anaesthetized cats. Recordings of carotid sinus nerve impulses allowed precise timing of the stimulus.2. Stimulation of the carotid body had a rapid effect on air flow, tidal volume and phrenic discharge rate only if given during inspiration. Increases in tidal volume and peak phrenic discharge occurred only if stimulation was applied during the last half of inspiration. Stimulation during expiration had no effect on the form or magnitude of subsequent breaths.3. Depression of the carotid body by NH(4)OH led to decreased tidal volume and phrenic discharge if it occurred during inspiration but had no effect if it occurred during expiration.4. Stimuli in expiration led to a prolongation of expiration. Stimuli in late inspiration caused prolongation of both inspiration and expiration.5. All of the effects noted were eliminated by bilateral carotid body denervation.6. The findings are similar to those following electrical stimulation of the carotid sinus nerve and are attributable to modulation of carotid body signals by the central respiratory neurones.     

Changes in the electrical activity of the respiratory muscles of cats during coughing

Summary Acute experiments were carried out on cats. Coughing was induced mechanically by the application of a nylon thread to the mucosa of the nasopharynx and the laryngeal area or to the bifurcation of the trachea and bronchi Electrical activity of the inspiratory and expiratory muscles became much more intense during the cough. Inspiratory activity was predominant during a cough induced by mechanical stimulation of the nasopharynx or of the larynx. The reciprocal relationship between inspiration and expiration was disturbed. In this type of cough the electrical activity of the expiratory muscles was increased at a time when the intrapleural pressure failed to indicate active respiration. When the cough was caused by mechanical stimulation of the mucosa at the bifurcation of the bronchi action potentials of large amplitude and high frequency occurred in long groups of discharges, in which expiratory activity prevailed. Under such conditions the normal relationship between inspiration and expiration were maintained. (Presented by Active Member MAN SSSR, V. V. Parin) Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 6,No. 11, pp. 24–27, November, 1963.     

Influence of rubrospinal tract and the adjacent mesencephalic reticular formation on the activity of medullary respiratory neurons and the phrenic nerve discharge in the rabbit

Suprapontine brain sites acting on the central respiratory system have been demonstrated to give rise to inspiratory as well as expiratory facilitatory effects. In the present study the inspiratory inhibitory effect which has been reported in the cat to be elicited consistently by electrical stimulation of the rubrospinal tract and the adjacent mesencephalic reticular formation was examined in the urethane-anaesthetized rabbit. Stimulation of these sites with single electrical shocks of moderate intensity induced a short latency (onset after 3.0 ms) transient (duration: 29 ms) inhibition of the phrenic nerve activity (PHR). Short volleys of stimuli applied in mid- to late-inspiration led to a premature off-switch of inspiration. The extracellularly recorded discharge activity of the different types of medullary respiration-related units (RRU) reflected these alterations, accordingly. Axonal connections of RRU with mesencephalic structures were evaluated. Examination of orthodromic responses of medullary RRU to stimulation of this pathway revealed that most bulbospinal inspiratory neurons (10 out of 13) were paucisynaptically inhibited after short latency (at least 1.2 ms). The conduction time from bulbospinal inspiratory neurons to the recording site of PHR was 1.6 ms. Thus, a disynaptic pathway — including bulbospinal inspiratory neurons — is suggested inducing inspiratory inhibition 3.0 ms after single shock midbrain stimulation. This inhibition results in disfacilitation of phrenic motoneurons. The fact that extensive electrolytic lesions of the pneumotaxic center in rostral pons did not abolish the observed inspiratory inhibitions excludes these structures from being involved. A direct pathway from the red nucleus and the adjacent reticular formation to phrenic nuclei of the spinal cord, however, can not be excluded from being involved in the demonstrated inspiratory inhibition. The described effects may play a role in behavioral or voluntary control of respiration.     

Rostrocaudal distribution of spinal respiratory motor activity in an in vitro neonatal rat preparation

The distribution of inspiratory and expiratory activities among rib-cage muscles was examined using isolated brainstem-spinal cord-rib preparations from neonatal rats. Expiratory activity was evoked by decreasing perfusate pH from 7.4 to 7.1. All internal intercostal muscles (IIMs) in the first to eleventh intercostal spaces showed expiratory bursts. Although the IIMs in the more caudal interspaces exhibited expiratory bursts for as long as the low pH solution was present in all preparations, the expiratory bursts obtained from the IIMs in the rostral interspaces gradually disappeared even under low pH conditions in about half the preparations, suggesting that the more caudal IIMs play the greater role in expiration. All thoracic ventral roots examined from T1VR-T11VR, but not T13VR, exhibited overt inspiratory bursts under normal pH conditions. Low pH solution induced additional expiratory bursts in all thoracic VRs. The ratio of the integral of the absolute electrical voltage during the expiratory phase to that during the inspiratory phase increased progressively and significantly from the rostral to the caudal interspaces. These results accord well with previous ones in mammals in vivo. Hence, the neuronal mechanisms necessary for a rostrocaudal gradient in spinal respiratory motor outputs seem to be preserved in this in vitro preparation.     

The bulbar network of respiratory neurons during apneusis induced by a blockade of NMDA receptors

Summary Our aim was to study the mechanisms producing the transition from the inspiratory phase to the expiratory phase of the breathing cycle. For this purpose we observed the changes affecting the discharge patterns and excitabilities of the different types of respiratory neurons within the respiratory network in cat medulla, after inducing an apneustic respiration with the N-methyl-D-aspartate (NMDA) antagonist MK-801 given systemically. Respiratory neurons were recorded extracellularly through the central barrel of multibarrelled electrodes, in the ventral respiratory area of pentobarbital-anesthetized, vagotomized, paralyzed and ventilated cats. Inhibitions exerted on each neuron by the presynaptic pools of respiratory neurons were revealed when the neuron was depolarized by an iontophoretic application of the excitatory amino-acid analogue quisqualate. Cycle-triggered time histograms of the spontaneous and quisqualate-increased discharge of respiratory neurons were constructed in eupnea and in apneusis induced with MK-801. During apneustic breathing, the activity of the respiratory neuronal network changed throughout the entire respiratory cycle including the post-inspiratory phase, and the peak discharge rates of all types of respiratory neurons, except the late-expiratory type, decreased. During apneusis, the activity of the post-inspiratory neuronal pool, the post-inspiratory depression of other respiratory neurons, and the phrenic nerve after-discharge were reduced (but not totally suppressed), whereas the discharge of some post-inspiratory neurons shifted into the apneustic plateau. The shortened post-inspiration (stage 1 of expiration) altered the organization of the expiratory phase. Late-expiratory neurons (stage 2 of expiration) discharged earlier in expiration and their discharge rate increased. The inspiratory on-switching was functionally unaffected. Early inspiratory neurons of the decrementing type retained a decrementing pattern followed by a reduced discharge rate in the apneustic plateau, whereas early-inspiratory neurons of the constant type maintained a high discharge rate throughout the apneustic plateau. Inspiratory augmenting neurons, late-inspiratory and offswitch neurons also discharged throughout the apneustic plateau. During the apneustic plateau, the level of activity was constant in the phrenic nerve and in inspiratory neurons of the early-constant, augmenting, and late types. However, progressive changes in the activity of other neuronal types demonstrated the evolving state of the respiratory network in the plateau phase. There was a slowed but continued decrease of the activity of early-inspiratory decrementing neurons, accompanied by an increasing activity and/or excitability of off-switch, postinspiratory and late-expiratory neurons. In apneusis there was a decoupling of the duration of inspiration and expiration. The variability of inspiratory duration increased five-fold whereas the variability of expiration was unchanged. We conclude that in the apneustic state, (1) inspiratory on-switching and the successive activation of the different inspiratory neuronal types are preserved; (2) near the end of the inspiratory ramp, the reversible phase of inspiratory off-switching is prolonged, producing the apneustic plateau, and (3) the irreversible phase of offswitching is impaired by a reduced activity of postinspiratory neurons. These results support the 3-phase model of respiratory rhythm generation, in which key roles are played by early-inspiratory and post-inspiratory neurons.