电刺激家兔迷走神经中枢端诱导的黑-伯反射中的非联合型学习现象

本文旨在研究电刺激家兔迷走神经诱导的黑-伯（Hering-Breuer,HB）反射中的学习和记忆现象。选择性电刺激家兔迷走神经中枢端（频率10～100Hz,强度20～60μA,波宽0．3ms,持续60s）,观察对膈神经放电的影响。以不同频率电刺激家兔迷走神经可模拟HB反射的两种成分,即类似肺容积增大所致抑制吸气的肺扩张反射和类似肺容积缩小所致加强吸气的肺萎陷反射。（1）长时高频（≥40Hz,60s）电刺激迷走神经可模拟呼吸频率减慢,呼气时程延长的肺扩张反射。随着刺激时间的延长,膈神经放电抑制的程度逐渐衰减,表现为呼吸频率的减慢（主要由呼气时程延长所致）在刺激过程中逐渐减弱或消失,显示为适应性或“习惯化”的现象;刺激结束时呼吸运动呈现反跳性增强,表现为一过性的呼气时程缩短,呼吸频率加快,然后才逐渐恢复正常。长时低频（〈40Hz,60s）电刺激迷走神经可模拟呼吸频率加快、呼气时程缩短的肺萎陷反射。随着刺激时间的延长,膈神经放电增强的程度逐渐衰减,同样表现出“习惯化”现象;刺激结束后,膈神经放电不是突然降低,而是继续衰减,表现为呼气时程逐渐延长,呼吸频率逐渐减慢,直至恢复到前对照水平,表现了刺激后的短时增强效应。（2）HB反射的适应性或“习惯化”程度反向依赖于刺激强度和刺激频率,表现为随着刺激强度和频率的增加,膈神经放电越远离正常基线水平,即爿惯化程度减弱。结果表明,家兔HB反射具有“习惯化”这一非联合型学习现象,反映与其有关的呼吸神经元网络具有突触功能的可翅性,呼吸的中枢调控反射具有一定的适应性。     

Phasic pulmonary stretch receptor feedback modulates both eupnea and gasping in an in situ rat preparation

The perfused in situ juvenile rat preparation produces patterns of phrenic discharge comparable to eupnea and gasping in vivo. These ventilatory patterns differ in multiple aspects, including most prominently the rate of rise of inspiratory activity. Although we have recently demonstrated that both eupnea and gasping are similarly modulated by a Hering-Breuer expiratory-promoting reflex to tonic pulmonary stretch, it has generally been assumed that gasping was unresponsive to afferent stimuli from pulmonary stretch receptors. In the present study, we recorded eupneic and gasplike efferent activity of the phrenic nerve in the in situ juvenile rat perfused brain stem preparation, with and without phrenic-triggered phasic pulmonary inflation. We tested the hypothesis that phasic pulmonary inflation produces reflex responses in situ akin to those in vivo and that both eupnea and gasping are similarly modulated by phasic pulmonary stretch. In eupnea, we found that phasic pulmonary inflation decreases inspiratory burst duration and the period of expiration, thus increasing burst frequency of the phrenic neurogram. Phasic pulmonary inflation also decreases the duration of expiration and increases the burst frequency during gasping. Bilateral vagotomy eliminated these changes. We conclude that the neural substrate mediating the Hering-Breuer reflex is retained in the in situ preparation and that the brain stem circuitry generating the respiratory patterns respond to phasic activation of pulmonary stretch receptors in both eupnea and gasping. These findings support the homology of eupneic phrenic discharge patterns in the reduced in situ preparation and eupnea in vivo and disprove the common supposition that gasping is insensitive to vagal afferent feedback from pulmonary stretch receptor mechanisms.     

Tonic pulmonary stretch receptor feedback modulates both eupnea and gasping in an in situ rat preparation

The perfused in situ juvenile rat preparation produces phrenic discharge patterns comparable to eupnea and gasping in vivo. These ventilatory patterns of eupnea and gasping differ in multiple aspects, including most prominently the rate of rise of inspiratory activity. Because gasping, but not eupnea, appeared similar after vagotomy in spontaneous breathing preparations, it has been assumed that gasping was unresponsive to afferent stimuli from pulmonary stretch receptors. In the present study, efferent activity of the phrenic nerve was recorded during eupnea and gasping in the in situ juvenile rat preparation. Gasping was induced in hypoxic-hypercapnia or ischemia. An increase in the pressure of tonic lung inflation from 1 to 10 cmH2O caused a prolongation of the duration between phrenic bursts in both eupnea or gasping. Bilateral vagotomy eliminated these changes. We conclude that the neural substrate mediating the Hering-Breuer reflex is retained in the in situ preparation and that the brain stem circuitry generating the respiratory patterns responds to tonic activation of pulmonary stretch receptors in a similar manner in eupnea and gasping. These findings support the homology of eupnea-like phrenic discharge patterns in the reduced in situ preparation and eupnea in vivo and disprove the common supposition that gasping is insensitive to vagal afferent feedback from pulmonary stretch receptor mechanisms.     

Effects of potassium channel blockers on hyperinflation-induced rapidly adapting pulmonary stretch receptor stimulation in the rabbit.

The effects of K+ channel blockers, such as 4-aminoprydine (4-AP) and tetraethylammonium (TEA), on the excitatory responses of rapidly adapting pulmonary stretch receptor (RAR) activity to hyperinflation (inflation volume=3 tidal volumes) were investigated in anesthetized, artificially ventilated rabbits after vagus nerve section. The changes in the RAR adaptation index (AI) produced by constant-pressure (approximately 30 cmH2O, 29.7+/-0.2 cmH2O) inflation of the lungs were also examined before and after pretreatment with 4-AP and TEA. The administration of 4-AP (0.7 and 2.0 mg/kg) potentiated hyperinflation-induced RAR stimulation in a dose-dependent manner. During hyperinflation after 2.0 mg/kg 4-AP administration the discharge of RARs showed a relatively regular firing pattern in both inflation and deflation phases. The RAR AI values during constant-pressure inflation of the lungs were significantly reduced by 4-AP treatment (2.0 mg/kg). TEA treatment (2.0 and 7.0 mg/kg) did not significantly alter either the excitatory response of RAR activity to hyperinflation or the RAR AI values seen during constant-pressure inflation of the lungs. These results suggest that during hyperinflation in in vivo experiments on rabbits, RARs may be maintained at a lower activity by opening the 4-AP-sensitive K+ channels on the receptor endings, which can determine accommodation of the receptor discharge.     

Inspiratory rhythm in airway smooth muscle tone

In anesthetized paralyzed open-chested cats ventilated with low tidal volumes at high frequency, we recorded phrenic nerve activity, transpulmonary pressure (TPP), and either the tension in an upper tracheal segment or the impulse activity in a pulmonary branch of the vagus nerve. The TPP and upper tracheal segment tension fluctuated with respiration, with peak pressure and tension paralleling phrenic nerve activity. Increased end-tidal CO2 or stimulation of the carotid chemoreceptors with sodium cyanide increased both TPP and tracheal segment tension during the increased activity of the phrenic nerve. Lowering end-tidal CO2 or hyperinflating the lungs to achieve neural apnea (lack of phrenic activity) caused a decrease in TPP and tracheal segment tension and abolished the inspiratory fluctuations. During neural apnea produced by lowering end-tidal CO2, lung inflation caused no further decrease in tracheal segment tension and TPP. Likewise, stimulation of the cervical sympathetics, which caused a reduction in TPP and tracheal segment tension during normal breathing, caused no further reduction in these parameters when the stimulation occurred during neural apnea. During neural apnea the tracheal segment tension and TPP were the same as those following the transection of the vagi or the administration of atropine (0.5 mg/kg). Numerous fibers in the pulmonary branch of the vagus nerve fired in synchrony with the phrenic nerve. Only these fibers had activity which paralleled changes in TPP and tracheal tension. We propose that the major excitatory input to airway smooth muscle arises from cholinergic nerves that fire during inspiration, which have preganglionic cell bodies in the ventral respiratory group in the region of the nucleus ambiguus and are driven by the same pattern generators that drive the phrenic and inspiratory intercostal motoneurons.     

Phase locking of the respiratory rhythm in cats to a mechanical ventilator

Mechanical ventilation of paralyzed, pentobarbital-anesthetized adult cats was performed while recording phrenic nerve activity. The periodic changes in lung volume owing to mechanical ventilation affected the rhythm of central respiratory activity, resulting in a variety of regular and irregular patterns of coupling between respiratory system output, monitored by phrenic activity, and the mechanical ventilator. Phase-locked patterns, in which phrenic burst onset occurred at specific and repetitive phase(s) of the mechanical ventilator, with ratios of ventilator frequency: phrenic burst frequency of 1:2, 1:1, 3:2, 2:1, and 3:1 were observed. Regular and irregular patterns occurred over specific ranges of frequency and volume of the mechanical ventilator. A careful study was made of the 1:1 phase locking as the frequency and inflation volume of the mechanical ventilator were changed. The inspiratory time (TI) was defined as the interval between the time when phrenic activity began to rise and the onset of its rapid decline, and the expiratory time (TE) as the time between inspirations. In the 1:1 phase-locking region, as the frequency of the ventilator was increased both TI and TE decreased, and the phase of phrenic onset in the ventilator cycle changed. During ventilation with frequencies higher than the intrinsic phrenic frequency (initial burst frequency of phrenic activity with the ventilator turned off) inspiratory activity was prematurely terminated by lung inflation (Hering-Breuer inspiratory inhibitory reflex). During ventilation with frequencies lower than the intrinsic phrenic frequency, the onset of phrenic activity was delayed (TE was prolonged) by lung inflation (Hering-Breuer expiratory promoting reflex).     

Influence of pulmonary inflations on discharge patterns of phrenic motoneurons

The purpose of this study was to assess the influence of pulmonary inflations on activities of single phrenic motoneurons. Studies were performed in decerebrate and paralyzed cats; activities of phrenic nerve and single phrenic motoneurons were recorded. Animals were ventilated with a servo-respirator which produced alterations in tracheal pressure in parallel with changes in integrated activity of the phrenic nerve. At end-tidal fractional concentrations of CO2 of 0.05, phrenic motoneurons were distributed into "early" and "late" populations, depending on time of onset of activity. During the late stages of neural inspiration, differences in levels of integrated activity of the phrenic nerve became evident between cycles with and without lung inflations. At a time approximating 90% of the inspiratory duration during inflations, integrated phrenic activity was higher for cycles with inflation. Concomitantly, with lung inflations, the discharge frequencies of early phrenic motoneurons were lower, and late motoneurons began to discharge sooner than when inflations were withheld. Similar results were obtained in hypercapnia. We conclude that reflexes activated by pulmonary inflations may produce augmentation, as well as inhibition of phrenic motoneuronal activities. Factors responsible for eliciting these reflex augmentations and inhibitions are discussed.     

Effects of high-frequency oscillatory ventilation on vagal and phrenic nerve activities

This study was undertaken to define the mechanism for the respiratory inhibition observed during high-frequency oscillatory ventilation (HFOV). The effects of HFOV on the activities of single units in the vagus (Vna) and phrenic nerves (Pna) were examined in pentobarbital-anesthetized dogs. The animals were either ventilated by intermittent positive-pressure ventilation (IPPV) with and without positive end-expiratory pressure (PEEP), or by HFOV at a frequency of 25 Hz and pump displacement volume of 3 ml/kg. In 13 vagal units the Vna was much higher during HFOV than during IPPV or airway occlusion at a matched airway pressure. Ten units in the phrenic nerves were examined, and Pna (expressed as bursts/min) was attenuated by HFOV in all of them. In four of them, the effect of cooling the vagi to 8-10 degrees C on Pna was examined, and it was found that HFOV failed to alter the Pna. We conclude that 1) HFOV stimulates the pulmonary vagal afferent fibers continuously and to a degree greater than that due to static lung inflation and increased airway pressure and 2) the increased vagal activity during HFOV probably causes phrenic nerve activity inhibition.     

Medullary lateral tegmental field: control of respiratory rate and vagal lung inflation afferent influences on sympathetic nerve discharge

We used spectral analysis and event-triggered averaging to determine the effects of chemical inactivation of the medullary lateral tegmental field (LTF) on 1) the relationship of intratracheal pressure (ITP, an index of vagal lung inflation afferent activity) to sympathetic nerve discharge (SND) and phrenic nerve activity (PNA) and 2) central respiratory rate in paralyzed, artificially ventilated dial-urethane-anesthetized cats. ITP-SND coherence value at the frequency of artificial ventilation was significantly (P<0.05; n=18) reduced from 0.73+/-0.04 (mean+/-SE) to 0.24+/-0.04 after bilateral microinjection of muscimol into the LTF. Central respiratory rate was unexpectedly increased in 12 of these experiments (0.28+/-0.03 vs. 0.95+/-0.25 Hz). The ITP-PNA coherence value was variably affected by chemical inactivation of the LTF. It was unchanged when central respiratory rate was also not altered, decreased when respiratory rate was increased above the rate of artificial ventilation, and increased when respiratory rate was raised from a value below the rate of artificial ventilation to the same frequency as the ventilator. Chemical inactivation of the LTF increased central respiratory rate in four of six vagotomized cats but did not significantly affect the PNA-SND coherence value. These data demonstrate that the LTF 1) plays a critical role in mediating the effects of vagal lung inflation afferents on SND but not PNA, 2) helps maintain central respiratory rate in the physiological range, but 3) is not involved in the coupling of central respiratory and sympathetic circuits.     

Adaptation to reflex effects of prolonged lung inflation

Adaptation to the reflex effects of sustained changes in lung volume on inspiratory duration (TI), expiratory duration (TE), and the phrenic neurogram was examined. Test inflations in gallamine-paralyzed dogs anesthetized with pentobarbital sodium were made during a 6-min trial while the animal was not ventilated: 2 min at functional residual capacity (FRC), 2 min at elevated airway pressure, and 2 min back at FRC. The dogs were hyperoxygenated and arterial PCO2 was kept constant by an infusion of tris (hydroxymethyl) aminomethane. The maintained inflations produced minimal changes in TI. On return to FRC, TI was prolonged in proportion to the magnitude of the prior inflation. In contrast, inflation produced marked prolongation of TE, which then adapted back toward preinflation values. On return to FRC, TE shortened initially to values below control. This shortening increased with greater prior lung inflations. The times to reestablish steady-state values upon return to FRC differed for TI (14.8 +/- 4.6 s) and TE (33.8 +/- 12.7 s). The magnitude of the phrenic neurogram at a fixed time from onset of inspiration and its slope were unchanged with inflation. These results indicate that respiratory phase durations are influenced not only by pulmonary afferent input within each respiratory cycle but also by prior vagal afferent activity that engages central processes with long, although different, time constants. Afferent input to the slow central process controlling TI is not gated to only one phase of the respiratory cycle.     

Reductions of neural activities to upper airway muscles after elevations in static lung volume.

We evaluated the hypothesis that the tonic discharge of pulmonary stretch receptors significantly influences the respiratory-modulated activities of cranial nerves. Decerebrate and paralyzed cats were ventilated with a servo-respirator, which produced changes in lung volume in parallel with integrated phrenic activity. Activities of the facial, hypoglossal, and recurrent laryngeal nerves and nerves to the thyroarytenoid muscle and triangularis sterni were recorded. After a stereotyped pattern of lung inflation, tracheal pressure was held at 1, 2, 4, or 6 cmH2O during the subsequent ventilatory cycle. Increases in tracheal pressure caused progressive reductions in both inspiratory and expiratory cranial nerve activities and progressive elevations in triangularis sterni discharge; peak levels of phrenic activity declined modestly. Similar changes were observed in normocapnia and hypercapnia. We conclude that the tonic discharge of pulmonary stretch receptors is an important determinant of the presence and magnitude of respiratory-modulated cranial nerve activity. This reflex mechanism may maintain upper airway patency and also regulate expiratory airflow.     

Respiratory arrhythmias and airway CO2, lung receptors, and central inspiratory activity

The purpose of this study was to determine whether hypocapnia affects heart rate secondary to an effect on pulmonary receptors. Dogs were anesthetized and placed on cardiopulmonary bypass. Interrelationships among airway CO2, central inspiratory activity, and lung receptor effects on respiratory-related heart rate changes (respiratory arrhythmias) were studied after vagal efferent activity was increased secondary to baroreceptor stimulation. Hypocapnia, isolated to the lungs, produced an increase in the magnitude of the respiratory arrhythmias observed. Two mechanisms may produce these results. Hypocapnia affects pulmonary receptors, which 1) reflexly alter heart rate and 2) modulate breathing frequency, thus altering the dynamics of the respiratory arrhythmias that were produced. The results also suggested that the reflex increase in heart rate in response to lung inflation and the Hering-Breuer expiratory-facilitatory reflex are either produced by different pulmonary receptors or by the same pulmonary receptors but may be mediated by different central mechanisms.     

Reflexes from the lungs and airways: historical perspective.

Historical aspects of respiratory reflexes from the lungs and airways are reviewed, up until about 10 yr ago. For most of the 19th century, the possible reflex inputs into the "respiratory center," the position of which had been identified, were very speculative. There was little concept of reflex control of the pattern of breathing. Then, in 1868, Breuer published his paper on "The self-steering of respiration via the Nervus Vagus." For the first time this established the role of vagal inflation and deflation reflexes in determining the pattern of breathing. Head later extended Breuer's work, and Kratschmer laid a similar basis for reflexes from the nose and larynx. Then, 50-60 yr later, the development of the thermionic valve and the oscilloscope allowed recording action potentials from single nerve fibers in the vagus. In 1933, Adrian showed that slowly adapting pulmonary stretch receptors were responsible for the inflation reflex. Later, Knowlton and Larrabee described rapidly adapting receptors and showed that they mediated deep augmented breaths and the deflation reflex. Still later, it was established that rapidly adapting receptors were, at least in part, responsible for cough. In 1954, Paintal began his study of C-fiber receptors (J receptors), work greatly extended by the Coleridges. Since approximately 10 yr ago, when the field of this review stops, there has been an explosion of research on lung and airway receptors, many aspects of which are dealt with in other papers in this series.     

Entrainment of respiratory rhythm to respiratory oscillations of arterial PCO2 in vagotomized dogs.

The aim of this study was to demonstrate that the medullary respiratory rhythm generator is capable of entraining to respiratory oscillations of arterial PCO2 (CO2 oscillations). We used 10 anesthetized, paralyzed, vagotomized, and mechanically ventilated dogs. First, rate of mechanical ventilation was manually adjusted so that it matched the dog's spontaneous respiratory rate, which established a constant phase relationship between the mechanical ventilation and the burst of phrenic neurogram (initial phase). Then this phase relationship was temporally disturbed by a brief electrical stimulation of the superior laryngeal nerve (SLN). In the control group, the initial phase and the steady-state phase relationship after SLN stimulation were randomly distributed within the phase plane, implying no interaction between the respiratory center and mechanical ventilation. In contrast, when CO2 output from the lung was increased 2.6-fold above the control level by venous CO2 loading, the initial phase and the steady-state phase after SLN stimulation were locked in such a way that the onset of the burst of phrenic neurogram coincided with the peak of CO2 oscillations. This was not demonstrated when the dog was made hyperoxic. We therefore conclude that the respiratory center could entrain to phasic chemical afferent inputs originating from CO2 oscillations, provided they are considerably amplified.     

兔心迷走神经传出放电的活动特征

兔心迷走神经传出放电有三种类型:1.与后膈神经传出发放同步的节律性放电。这种节律性发放包含两个时相,第一时相大致与膈神经传出放电同时起止,第二时相在膈神经传出发放后期或发放终止时出现。2.持续性放电,出现在上述节律性放电的间歇期。3.偶然出现的高幅高频暴发放电。这种放电出现时,膈神经传出放电即受到明显的压抑。开放预先夹闭的颈总动脉使心迷走神经传出放电增强。窒息、静脉注射肾上腺素使心迷走神经传出放电增强,心率减慢;扩张肺、过度通气、吸入亚硝酸异戊酯使心迷走神经传出放电减少,心率增快。     

Reinnervation of pulmonary stretch receptors

The Breuer-Hering reflex (BHR) reappears 12-14 wk after surgical lung denervation in beagle dogs (J. Appl. Physiol. 54: 1451-1456, 1983). To demonstrate that this is due to reinnervation of pulmonary stretch receptors, we recorded nerve activity from regenerated branches of the left vagus nerve in five beagle dogs. Ten days postdenervation the BHR was absent, whereas by 19 mo it was clearly present. Multifiber pulmonary afferent activity was observed in all five dogs with single-fiber activity observed in three. Sectioning the right vagus nerve did not alter the BHR, but sectioning all the regenerated branches of the left vagus abolished the reflex. In two additional dogs studied 17 mo postsurgery, recordings were made from few fiber nerve bundles of the left cervical vagus. Nerve activity was increased during gentle stroking of the surface of the left upper and lower lobes, indicating receptive fields in both lobes. These data demonstrate that reinnervation of pulmonary stretch receptors does occur and provides evidence that reinnervation of these receptors is responsible for return of the BHR after pulmonary denervation.     

Properties of reversible graded inhibition of phrenic nerve activity by pulmonary afferents

Reversible graded inhibition of phrenic nerve activity (PNA) was observed during short, low volume lung inflations in chloralose anaesthetized, paralyzed cats. The strength of the inhibitory effect rose with the volume of inflation in a manner suggesting non-linearity. The volume threshold for the first detectable inhibition decreased with increasing delay between onest of inspiration and lung inflation. The differences between the threshold curve for different air flows were not significant. The recovery of PNA from transient inhibition was not immediate and this shows that lung inflations might activate a central inhibitory mechanism, the action of which could outlast the activation period of lung receptors. It is suggested that pulmonary stretch receptors (PSR) are responsible for the observed reactions. The present results indicate that the theory of "all or none" action of PSR on inspiratory activity is not valid for all experimental conditions, and that PSR are capable of continuous control of PNA pattern.     

Effects of pulse lung inflation on chest wall expiratory motor activity.

The effects of pulse lung inflation (LI) on expiratory muscle activity and phase duration (Te) were determined in anesthetized, spontaneously breathing dogs (n = 20). A volume syringe was used to inflate the lungs at various times during the expiratory phase. The magnitude of lung volume was assessed by the corresponding change in airway pressure (Paw; range 2-20 cmH(2)O). Electromyographic (EMG) activities were recorded from both thoracic and abdominal muscles. Parasternal muscle EMG was used to record inspiratory activity. Expiratory activity was assessed from the triangularis sterni (TS), internal intercostal (IIC), and transversus abdominis (TA) muscles. Lung inflations <7 cmH(2)O consistently inhibited TS activity but had variable effects on TA and IIC activity and expiratory duration. Lung inflations resulting in Paw values >7 cmH(2)O, however, inhibited expiratory EMG activity of each of the expiratory muscles and lengthened Te in all animals. The responses of expiratory EMG and Te were directly related to the magnitude of the lung inflation. The inhibition of expiratory motor activity was independent of the timing of pulse lung inflation during the expiratory phase. The inhibitory effects of lung inflation were eliminated by bilateral vagotomy and could be reproduced by electrical stimulation of the vagus nerve. We conclude that pulse lung inflation resulting in Paw between 7 and 20 cmH(2)O produces a vagally mediated inhibition of expiratory muscle activity that is directly related to the magnitude of the inflation. Lower inflation pressures produce variable effects that are muscle specific.     

Pulmonary receptors in reptiles: discharge patterns of receptor populations in snakes versus turtles

This study examines the effects of lung inflation/deflation with and without CO2 on the entire population of pulmonary receptors in the vagus nerve in two species of snakes and two species of turtles. We asked the question, "how does the response of the entire mixed population of pulmonary stretch receptors (PSR) and intrapulmonary chemoreceptors (IPC) in species possessing both differ from that in species with only PSR"? This was studied under conditions of artificial ventilation with the secondary goal of extending observations on the presence/absence of IPC to a further three species. Our results indirectly illustrate the presence of IPC in the Burmese python and South American rattlesnake but not the side necked turtle, adding support to the hypothesis that IPC first arose in diapsid reptiles. In both species of snake, CO2-sensitive discharge (presumably from IPC) predominated almost to the exclusion of CO2-insensitive discharge (presumably arising from PSR) while the opposite was true for both species of turtle. The data suggest that for animals breathing air under conditions of normal metabolism there is little to distinguish between the discharge profiles of the total population of receptors arising from the lungs in the different groups. Interestingly, however, under conditions of elevated environmental CO2 most volume-related feedback from the lungs is abolished in the two species of snakes, while under conditions of elevated metabolic CO2, it is estimated that volume feedback from the lungs would be enhanced in these same species.     

Analysis of postinspiratory activity of phrenic motoneurons with chemical and vagal reflexes

We examined the effects of chemical and reflex drives on the postinspiratory inspiratory activity (PIIA) of phrenic motoneurons using a single-fiber technique. Action potentials from "single" fibers were recorded from the C5 phrenic root together with contralateral mass phrenic activity (also from C5) in anesthetized, paralyzed, and artificially ventilated cats with intact vagus and carotid sinus nerves. Nerve fibers were classified as "early" or "late" based on their onset of discharge in relation to mass phrenic activity during hyperoxic ventilation. Only the early fibers displayed PIIA but not the late fibers, even when their activity began earlier in inspiration with increased chemical drives. Isocapnic hypoxia increased, whereas hyperoxic hypercapnia shortened the duration of PIIA. Pulmonary stretch and "irritant" receptors inhibited PIIA. Hypercapnia and stimulation of peripheral chemoreceptors by lobeline excited both early and late units to the same extent, but hypoxic ventilation had a less marked excitatory effect on late fiber activity. Irritant receptor activation increased the activity of early more than late fibers. Hyperoxic hyperventilation eliminated late phrenic fiber activity, whereas early fibers became tonically active. Bilateral vagotomy abolished this sustained discharge in eight of nine early units, suggesting the importance of vagal afferents in producing tonic firing during hyperventilation. These results suggest that early and late phrenic fibers have different responses to chemical stimuli and to vagally mediated reflexes; late units do not discharge in postinspiratory period, whereas early fibers do; the PIIA is not affected in the same way by various chemical and vagal inputs; and early units that exhibit PIIA display tonic activity with hyperoxic hypocapnia.