Motor responses to positive-pressure breathing in the developing opossum

The suckling opossum exhibits an expiration-phased discharge in abdominal muscles during positive-pressure breathing (PPB); the response becomes apparent, however, only after the 3rd-5th wk of postnatal life. The purpose of this study was to determine whether the early lack of activation represented a deficiency of segmental outflow to abdominal muscles or whether comparable effects were observed in cranial outflows to muscles of the upper airways due to immaturity of afferent and/or supraspinal pathways. Anesthetized suckling opossums between 15 and 50 days of age were exposed to PPB; electromyogram (EMG) responses in diaphragm and abdominal muscles were measured, along with EMG of larynx dilator muscles and/or upper airway resistance. In animals older than approximately 30 days of age, the onset of PPB was associated with a prolonged expiration-phased EMG activation of larynx dilator muscles and/or decreased upper airway resistance, along with expiratory recruitment of the abdominal muscle EMG. These effects persisted as long as the load was maintained. Younger animals showed only those responses related to the upper airway; in fact, activation of upper airway muscles during PPB could be associated with suppression of the abdominal motor outflow. After unilateral vagotomy, abdominal and upper airway motor responses to PPB were reduced. The balance between PPB-induced excitatory and inhibitory or disfacilitory influences from the supraspinal level on abdominal motoneurons and/or spinal processing of information from higher centers may shift toward net excitation as the opossum matures.     

Ventrolateral medullary respiratory network participation in the expiration reflex in the cat.

The expiration reflex is a distinct airway defensive response characterized by a brief, intense expiratory effort and coordinated adduction and abduction of the laryngeal folds. This study addressed the hypothesis that the ventrolateral medullary respiratory network participates in the reflex. Extracellular neuron activity was recorded with microelectrode arrays in decerebrated, neuromuscular-blocked, ventilated cats. In 32 recordings (17 cats), 232 neurons were monitored in the rostral (including B?tzinger and pre-B?tzinger complexes) and caudal ventral respiratory group. Neurons were classified by firing pattern, evaluated for spinal projections, functional associations with recurrent laryngeal and lumbar nerves, and firing rate changes during brief, large increases in lumbar motor nerve discharge (fictive expiration reflex, FER) elicited during mechanical stimulation of the vocal folds. Two hundred eight neurons were respiratory modulated, and 24 were nonrespiratory; 104 of the respiratory and 6 of the nonrespiratory-modulated neurons had altered peak firing rates during the FER. Increased firing rates of bulbospinal neurons and expiratory laryngeal premotor and motoneurons during the expiratory burst of FER were accompanied by changes in the firing patterns of putative propriobulbar neurons proposed to participate in the eupneic respiratory network. The results support the hypothesis that elements of the rostral and caudal ventral respiratory groups participate in generating and shaping the motor output of the FER. A model is proposed for the participation of the respiratory network in the expiration reflex.     

Ventrolateral medullary respiratory network and a model of cough motor pattern generation

The primaryhypothesis of this study was that the cough motor pattern is produced,at least in part, by the medullary respiratory neuronal network inresponse to inputs from "cough" and pulmonary stretch receptorrelay neurons in the nucleus tractus solitarii. Computer simulations ofa distributed network model with proposed connections from the nucleustractus solitarii to ventrolateral medullary respiratory neuronsproduced coughlike inspiratory and expiratory motor patterns. Predictedresponses of various "types" of neurons (I-DRIVER, I-AUG, I-DEC,E-AUG, and E-DEC) derived from the simulations were tested in vivo.Parallel and sequential responses of functionally characterizedrespiratory-modulated neurons were monitored during fictive cough indecerebrate, paralyzed, ventilated cats. Coughlike patterns in phrenicand lumbar nerves were elicited by mechanical stimulation of theintrathoracic trachea. Altered discharge patterns were measured in mosttypes of respiratory neurons during fictive cough. The resultssupported many of the specific predictions of our cough generationmodel and suggested several revisions. The two main conclusions were asfollows: 1) TheBötzinger/rostral ventral respiratory group neurons implicated inthe generation of the eupneic pattern of breathing also participate inthe configuration of the cough motor pattern.2) This altered activity ofBötzinger/rostral ventral respiratory group neurons istransmitted to phrenic, intercostal, and abdominal motoneurons via thesame bulbospinal neurons that provide descending drive during eupnea.

     

Respiratory muscle control during vomiting

The changes in thoracic and abdominal pressure that generate vomiting are produced by coordinated action of the major respiratory muscles. During vomiting, the diaphragm and external intercostal (inspiratory) muscles co-contract with abdominal (expiratory) muscles in a series of bursts of activity that culminates in expulsion. Internal intercostal (expiratory) muscles contract out of phase with these muscles during retching and are inactive during expulsion. The periesophageal portion of the diaphragm relaxes during expulsion, presumably facilitating rostral movement of gastric contents. Recent studies have begun to examine to what extent medullary respiratory neurons are involved in the control of these muscles during vomiting. Bulbospinal expiratory neurons in the ventral respiratory group caudal to the obex discharge at the appropriate time during (fictive) vomiting to activate either abdominal or internal intercostal motoneurons. The pathways that drive phrenic and external intercostal motoneurons during vomiting have yet to be identified. Most bulbospinal inspiratory neurons in the dorsal and ventral respiratory groups do not have the appropriate response pattern to initiate activation of these motoneurons during (fictive) vomiting. Relaxation of the periesophageal diaphragm during vomiting could be brought about, at least in part, by reduced firing of bulbospinal inspiratory neurons.     

Simulations of a ventrolateral medullary neural network for respiratory rhythmogenesis inferred from spike train cross-correlation

Connections among ventrolateral medullary respiratory neurons inferred from spike train analysis were incorporated into a model and simulated with the program SYSTM11 (MacGregor 1987). Inspiratory (I) and expiratory (E) neurons with augmenting (AUG) and decrementing (DEC) discharge patterns and rostral I-E/I neurons exhibited varying degrees of adaptation, but no endogenous bursting properties. Simulation parameters were adjusted so that respiratory phase durations, neuronal discharge patterns, and short-time scale correlations were similar to corresponding measurements from anesthetized, vagotomized, adult cats. Rhythmogenesis persisted when the strength of each set of connections was increased 100% over a smaller effective value. Changes in phase durations and discharge patterns caused by manipulation of connection strengths or population activity led to several predictions. (a) Excitation of the I-E/I population prolongs the inspiratory phase. (b) Rhythmic activity can be reestablished in the absence of I-E/I activity by unpatterned excitation of I-DEC and I-AUG neurons. (c) An increase in I-DEC neuron activity can cause an apneustic respiratory pattern. (d) A decrease in I-DEC neuron activity increases the slope of the inspiratory ramp and shortens inspiration. (e) Excitation of the E-DEC population prolongs the expiratory phase or produces apnea; inhibition of E-DEC neurons reduces expiratory time. (f) Excitation of E-AUG cells causes I-AUG neurons to exhibit a step rather than a ramp increase in firing rate at the onset of their active phase. The results suggest mechanisms by which the duration of each phase of breathing and neuronal discharge patterns may be regulated. Received: 24 February 1993/Accepted in revised form: 8 September 1993     

Medullary raphe neuron activity is altered during fictive cough in the decerebrate cat.

Chemical lesions in the medullary raphe nuclei region influence cough. This study examined whether firing patterns of caudal medullary midline neurons were altered during cough. Extracellular neuron activity was recorded with microelectrode arrays in decerebrated, neuromuscular-blocked, ventilated cats. Cough-like motor patterns (fictive cough) in phrenic and lumbar nerves were elicited by mechanical stimulation of the intrathoracic trachea. Discharge patterns of respiratory and nonrespiratory-modulated neurons were altered during cough cycles (58/133); 45 increased and 13 decreased activity. Fourteen cells changed firing rate during the inspiratory and/or expiratory phases of cough. Altered patterns in 43 cells were associated with the duration of, or extended beyond, the cough episodes. The different response categories suggest that multiple factors influence the discharge patterns during coughing: e.g., respiratory-modulated and tonic inputs and intrinsic connections. These results suggest involvement of midline neurons (i.e., raphe nuclei) in the cough reflex.     

Respiratory neuronal activity during apnea and other breathing patterns induced by laryngeal stimulation

Respiration cycles through three distinct phases (inspiration, postinspiration, and expiration) each having corresponding medullary cells that are excited during one phase and inhibited during the other two. Laryngeal stimulation is known to induce apnea in newborn animals, but the cellular mechanisms underlying this effect are not known. Intracellular recording of ventral respiratory group neurons was accomplished in intact anesthetized, paralyzed, and mechanically ventilated piglets. Apnea was induced by insufflation of the larynx with ammonia-saturated air, smoke, or water. Laryngeal insufflation induced phrenic nerve apnea, stimulation of postinspiratory neurons, and stable membrane potentials in inspiratory and expiratory cells consistent with postinspiratory inhibition. Usually the membrane potential of each neuronal type cycled through an expiratory level before onset of the first recovery breath. Variants of the apnea response, probably reflecting the aspiration reflex or sniffing, sneezing, coughing, and swallowing, were also observed. These latter patterns showed oscillation between inspiration and postinspiration without an apparent intervening stage II expiratory phase. However, stage II expiratory activity always preceded onset of the first ramp inspiration after such a pattern. These findings suggest that activation of postinspiratory mechanisms causes profound alterations in the respiratory pattern and that stage II expiration importantly modulates recovery of ramp inspiratory activity. The mechanism of this latter effect may be inhibition of early inspiratory neurons with consequent postinhibitory rebound.     

Respiratory rhythmicity in the cat.

Brain stem respiratory neuron activity in the cat was studied in relation to efferent outflow (phrenic discharge) under the influence of several forcing inputs: 1) CO2 tension: hypocapnia produces disappearance of firing in some neurons, and conversion of respiratory-modulated to continuous (tonic) firing in others. 2) Lung inflation: during the Bruer-Hering reflex, some neurons have "classical" responses and others have "paradoxical" responses (i.e., opposite in direction to peripheral discharge). 3) Electrical stimulation: stimulus trains to the pneumotaxic center region (rostral lateral pons) produce phase-switching, whose threshold is: a) sharp (indicating action of positive-feedback mechanisms), and b) dependent on timing of stimulus delivery (indicating continuous excitability changes during each respiratory phase). Auto- and crosscorrelation analysis revealed the existence of short-term interactions between: a) medullary inspiratory (I) neurons and phrenic motoneurons; b) pairs of medullary I neurons; c) medullary I neurons and expiratory (E) neurons. A model of the respiratory oscillator is presented, in which the processes of conversion of tonic to phasic activity and switching of the respiratory phases are explained by recurrent excitatory and inhibitory loops.     

Differing activities of medullary respiratory neurons in eupnea and gasping

Our purpose was to compare further eupneic ventilatory activity with that of gasping. Decerebrate, paralyzed, and ventilated cats were used; the vagi were sectioned within the thorax caudal to the laryngeal branches. Activities of the phrenic nerve and medullary respiratory neurons were recorded. Antidromic invasion was used to define bulbospinal, laryngeal, or not antidromically activated units. The ventilatory pattern was reversibly altered to gasping by exposure to 1% carbon monoxide in air. In eupnea, activities of inspiratory neurons commenced at various times during inspiration, and for most the discharge frequency gradually increased. In gasping, the peak discharge frequency of inspiratory neurons was unaltered. However, all commenced activities at the start of the phrenic burst and reached peak discharge almost immediately. The discharge frequencies of all groups of expiratory neurons fell in gasping, with many neurons ceasing activity entirely. These data are consistent with the hypothesis that brain stem mechanisms controlling eupnea and gasping differ fundamentally.     

Effects on breathing of rostral pons glutamate injection during opossum development

To determine whether pathways from the rostral pons, capable of influencing breathing, were present in immature mammals, the excitatory amino acid glutamate (sodium salt) was pressure injected in very small volumes into the rostral pons of suckling and adult opossums. The youngest animals tested were approximately 3 wk old (1.5-2.9 g). Animals were anesthetized with the thiobarbituric acid derivative, Inactin, and the electromyogram of the diaphragm was used to assess changes in breathing rhythm and ventilatory output. Glutamate concentrations of 50, 150, and 1,000 mM were injected into the rostral pons. Active sites were generally located between parabrachial and either lateral lemniscal or trigeminal nuclei. Effects of glutamate in opossums of all ages included changes in diaphragm activity and respiratory timing over several breaths. In the youngest animals, a very high incidence of apnea occurred as an initial response (17 of 20 sites) at the 1,000 mM concentration. The high incidence of apneic response in the youngest animals suggests that strong activation of rostral pontine neurons can more easily disrupt respiratory output; a physiological circumstance of such activation might include a diving response stimulated by trigeminal afferents.     

Differential recruitment of expiratory muscles during opossum development

Relationships between time-averaged electromyogram (EMG) discharge in abdominal (ABD) and lateralintercostal (IC) muscles (interspaces 1-10) were evaluated when Inactin-anesthetized supine opossums between 20 and 100 days of age were challenged by positive-pressure breathing (PPB) (3, 6, and 8 cmH2O). Expiratory activity upon initiation of PPB was observed in ABD muscles after the 30th postnatal day; recruitment of IC muscles requires further maturation. For example, at a PPB level of 6 cmH2O, animals up to 50-55 days of age recruited IC muscles from the lowest three interspaces on 44% of the occasions where ABD muscles were activated; in older animals the incidence of IC recruitment increased to 87%. Additionally, the occurrence of IC relative to ABD recruitment increased with increasing levels of PPB; IC muscles of highest interspaces (1-3) were activated less often at all pressures. At the onset of PPB, ABD muscles were usually recruited before IC muscles; this effect was more prominent in the younger animals. During the 5th min of PPB, ABD muscles were recruited earlier in expiration than IC muscles in the majority of animals at all ages. Since IC and ABD motor groups are activated from similar levels of the spinal cord, the delayed maturation of IC muscle responses to PPB may reflect developmental processes involving reflexes from the chest or abdomen, and/or may be a function of nonrespiratory utilization (i.e., postural) of ABD and IC muscles.     

Central pathway for spontaneous and prostaglandin E2-evoked cutaneous vasoconstriction

A reduction of heat loss to the environment through increased cutaneous vasoconstrictor (CVC) sympathetic outflow contributes to elevated body temperature during fever. We determined the role of neurons in the dorsomedial hypothalamus (DMH) in increases in CVC sympathetic tone evoked by PGE2 into the preoptic area (POA) in chloralose/urethane-anesthetized rats. The frequency of axonal action potentials of CVC sympathetic ganglion cells recorded from the surface of the tail artery was increased by 1.8 Hz following nanoinjections of bicuculline (50 pmol) into the DMH. PGE2 nanoinjection into the POA elicited a similar excitation of tail CVC neurons (+2.1 Hz). Subsequent to PGE2 into the POA, muscimol (400 pmol/side) into the DMH did not alter the activity of tail CVC neurons. Inhibition of neurons in the rostral raphé pallidus (rRPa) eliminated the spontaneous discharge of tail CVC neurons but only reduced the PGE2-evoked activity. Residual activity was abolished by subsequent muscimol into the rostral ventrolateral medulla. Transections through the neuraxis caudal to the POA increased the activity of tail CVC neurons, which were sustained through transections caudal to DMH. We conclude that while activation of neurons in the DMH is sufficient to activate tail CVC neurons, it is not necessary for their PGE2-evoked activity. These results support a CVC component of increased core temperature elicited by PGE2 in POA that arises from relief of a tonic inhibition from neurons in POA of CVC sympathetic premotor neurons in rRPa and is dependent on the excitation of CVC premotor neurons from a site caudal to DMH.     

Opiate slowing of feline respiratory rhythm and effects on putative medullary phase-regulating neurons

Opiates have effects on respiratory neurons that depress tidal volume and air exchange, reduce chest wall compliance, and slow rhythm. The most dose-sensitive opioid effect is slowing of the respiratory rhythm through mechanisms that have not been thoroughly investigated. An in vivo dose-response analysis was performed on medullary respiratory neurons of adult cats to investigate two untested hypotheses related to mechanisms of opioid-mediated rhythm slowing: 1) Opiates suppress intrinsic conductances that limit discharge duration in medullary inspiratory and expiratory neurons, and 2) opiates delay the onset and lengthen the duration of discharges postsynaptically in phase-regulating postinspiratory and late-inspiratory neurons. In anesthetized and unanesthetized decerebrate cats, a threshold dose (3 microg/kg) of the mu-opioid receptor agonist fentanyl slowed respiratory rhythm by prolonging discharges of inspiratory and expiratory bulbospinal neurons. Additional doses (2-4 microg/kg) of fentanyl also lengthened the interburst silent periods in each type of neuron and delayed the rate of membrane depolarization to firing threshold without altering synaptic drive potential amplitude, input resistance, peak action potential frequency, action potential shape, or afterhyperpolarization. Fentanyl also prolonged discharges of postinspiratory and late-inspiratory neurons in doses that slowed the rhythm of inspiratory and expiratory neurons without altering peak membrane depolarization and hyperpolarization, input resistance, or action potential properties. The temporal changes evoked in the tested neurons can explain the slowing of network respiratory rhythm, but the lack of significant, direct opioid-mediated membrane effects suggests that actions emanating from other types of upstream bulbar respiratory neurons account for rhythm slowing.     

The number and location of Fos-like immunoreactive neurons in the central gustatory system following electrical stimulation of the parabrachial nucleus in conscious rats

Electrical stimulation of the waist area (W) of the parabrachial nucleus (PBN) in conscious rats elicits stereotypical oromotor behaviors (Galvin et al. 2004). To identify neurons possibly involved in these behavioral responses, we used Fos immunohistochemistry to locate populations of neurons within central gustatory and oromotor centers activated by PBN stimulation. Dramatic increases in the numbers of Fos-like immunoreactive neurons were observed in the ipsilateral PBN, nucleus of the solitary tract (NST), and central amygdala. The increase in neurally-activated cells within the ventral subdivision (V) of the rostral NST is particularly noteworthy because of its projections to medullary oromotor centers. A modest increase in labeled neurons occurred bilaterally within the gustatory cortex. Although there were trends for an increase in Fos-labeled neurons in the gustatory thalamus and medullary reticular formation, most changes in labeled neurons in these areas were not statistically significant. Linear regression analysis revealed a relationship between the number of taste reactivity (TR) behaviors performed during PBN stimulation and the number of Fos-like immunoreactive neurons in the caudal PBN and V of the rostral NST. These data support a role for neurons in W of the PBN and the ventral rostral NST in the initiation of TR behaviors.     

Naloxone application to the ventrolateral medulla enhances the respiratory response to inspired carbon dioxide

Previous studies have shown that systemic administration of the opiate antagonist naloxone potentiates the ventilatory response to inspired carbon dioxide. The present study was designed to localize the site of action of naloxone for increasing the respiratory chemosensitivity to inhaled carbon dioxide (CO2) in cats. Naloxone applied topically to the caudal chemosensitive area on the ventral medullary surface (VMS) during hypercapnic breathing produced a 75% greater increase in minute ventilation than hypercapnic breathing alone. Furthermore, hypercapnic breathing produced a 200% increase in neuronal activity of VMS chemosensitive cells; this was further increased 120% by naloxone. It is concluded that naloxone increases the sensitivity of neurons in the caudal respiratory chemosensitive area of cats to hypercapnia, and that endogenous opiates may act as modulators at VMS chemosensitive sites during hypercapnic breathing.     

Responses of bulbospinal and laryngeal respiratory neurons to hypercapnia and hypoxia

The purpose was to evaluate activities of medullary respiratory neurons during equivalent changes in phrenic discharge resulting from hypercapnia and hypoxia. Decerebrate, cerebellectomized, paralyzed, and ventilated cats were used. Vagi were sectioned at left midcervical and right intrathoracic levels caudal to the origin of right recurrent laryngeal nerve. Activities of phrenic nerve and single respiratory neurons were monitored. Neurons exhibiting antidromic action potentials following stimulations of the spinal cord and recurrent laryngeal nerve were designated, respectively, bulbospinal or laryngeal. The remaining neurons were not antidromically activated. Hypercapnia caused significant augmentations of discharge frequencies for all neuronal groups. Many of these neurons had no change or declines of activity in hypoxia. We conclude that central chemoreceptor afferent influences are ubiquitous, but excitatory influences from carotid chemoreceptors are more limited in distribution among medullary respiratory neurons. Hypoxia will increase activities of neurons that receive sufficient excitatory peripheral chemoreceptor afferents to overcome direct depression by brain stem hypoxia. The possibility that responses of respiratory muscles to hypoxia are programmed within the medulla is discussed.     

Central respiratory pattern generation in the bullfrog, Rana catesbeiana

There are two components to breathing pattern generation the production of the pattern of neural discharge associated with individual breaths, and the pattern in which breaths are produced to effect ventilation. Bullfrogs typically breathe with randomly distributed breaths. When respiratory drive is elevated, breathing becomes more regular and often episodic. Studies on in vitro brainstem-spinal cord preparations of the adult bullfrog and in situ preparations of decerebrate, paralyzed, unidirectionally ventilated animals suggest that output from the central rhythm generator in frogs is conditional on receiving some input and that a host of central inputs remain even in the most reduced preparations. There appear to be descending inputs from sites in the dorsal brainstem just caudal to the optic chiasma that cluster breaths into episodes, a strong excitatory input caudal to this site but rostral to the origin of the Vth cranial nerve and, possibly, segmental rhythm generators throughout the medulla that are normally entrained to produce the normal breathing pattern. The data also suggest that the shape of the discharge pattern (augmenting, decrementing) and timing of outputs (alternating vs synchronous) associated with motor outflow during each breath are also dependent on the interconnections between these various sites.     

Influences of superior laryngeal afferent stimulation on expiratory activity in cats

The effects of superior laryngeal nerve (SLN) stimulation on the activity of the expiratory muscles and medullary expiration-related (ER) neurons were investigated in 24 pentobarbital-anesthetized cats. In some experiments the animals were also paralyzed and artificially ventilated. Sustained tetanic stimulation of SLN consistently caused an apneic response associated with the appearance of tonic CO2-dependent activity in the expiratory muscles and in ER neurons located in the caudal ventral respiratory group (VRG) and the B?tzinger complex. Single shocks or brief tetani at the same stimulation intensities failed to evoke excitatory responses in the expiratory muscles and in the vast majority of ER neurons tested. At higher stimulation strengths, single shocks or short tetani elicited excitatory responses in the expiratory muscles (20- to 35-ms latency) and in the majority of ER neurons of the caudal VRG (7.5- to 15.5-ms latency). These responses were obtained only during the expiratory phase and proved to be CO2 independent. On the contrary, only inhibitory responses were evoked in the activity of B?tzinger complex neurons. The observed tonic expiratory activity most likely represents a disinhibition phenomenon due to the suppression of inspiratory activity; activation of expiratory muscles at higher stimulation intensities appears to be a polysynaptic reflex mediated by ER neurons of the caudal VRG but not by B?tzinger complex neurons.     

Electrical stimulation of the posteromedial thalamus modulates breathing in unanesthetized fetal sheep.

Having previously shown that lesions in the posteromedial group of thalamic nuclei abolish hypoxic inhibition of fetal breathing, we devised this study to identify thalamic loci that depress breathing by focal stimulation of specific sectors of the caudal thalamus and adjacent structures. Multipolar electrode arrays consisting of a series of eight stimulation contacts at 1.25-mm intervals were implanted vertically through guide cannulae into the caudal diencephalon of 12 chronically catheterized fetal sheep (>0.8 term), and central neural tissue was stimulated between adjacent contacts. Each site was stimulated repeatedly with increasing current searching for spatial and stimulus strength parameters for a reliable alteration in respiratory rate. Respiratory period increased when stimulation involved areas of the parafascicular nuclear complex (Pf), which more than doubled the mean period compared with the baseline of 0.90 +/- 0.19 s. The change in respiratory period was due to an increase in expiratory time, whereas inspiratory time and breath amplitude were not significantly affected. Breathing period and expiratory time were also increased when the stimulations involved the intralaminar wing surrounding the mediodorsal nucleus, the rostral central gray, zona incerta, and ventral tegmental area. Reductions in respiratory frequency occurred less consistently, with stimulation involving surrounding zones including the sub-Pf, ventromedial nucleus, and ventrobasal nuclear complex. These findings support the hypothesis that a restricted area of the posteromedial thalamus (principally Pf) constitutes part of a neuronal circuitry that modulates respiratory motoneurons.     

Internal intercostal nerve discharges in the cat: influence of chemical stimuli

We studied the influence of central and peripheral chemoreceptor stimulation on the activities of the phrenic and internal intercostal (iic) nerves in decerebrate, vagotomized, and paralyzed cats with bilateral pneumothoraces. Whole iic nerves of the rostral thorax (T2-T5) usually discharged during neural inspiration, whereas those of the caudal thorax (T7-T11) were primarily active during neural expiration. Filaments of rostral iic nerves that terminated in iic muscles generally discharged during expiration, suggesting that inspiratory activity recorded in whole iic nerves may have innervated other structures, possibly parasternal muscles. All nerves were phasically active at hyperoxic normocapnia and increased their activities systematically with hypercapnia. Isocapnic hypoxia or intra-arterial NaCN injection consistently increased phrenic and inspiratory iic nerve activities. In contrast, expiratory iic nerve discharges were either decreased (10 cats) or increased (7 cats) by hypoxia. Furthermore, expiratory responses to NaCN were highly variable and could not be predicted from the corresponding response to hypoxia. The results show that central and peripheral chemoreceptor stimulation can affect inspiratory and expiratory motoneuron activities differentially. The variable effects of hypoxia on expiratory iic nerve activity may reflect a relatively weak influence of carotid body afferents on expiratory bulbospinal neurons. However, the possibility that the magnitude of expiratory motoneuron activity is influenced by the intensity of the preceding centrally generated inspiratory discharge is also discussed.