Synchronization of respiratory frequency by somatic afferent stimulation.

In cats anesthetized with chloralose-urethan, vagotomized, paralyzed, and artifically ventilated, superficial radial (cutaneous) and hamstring (muscle) nerve afferents were stimulated while phrenic nerve electrical activity was recorded. The results obtained with both types of nerves were similar. Stimulation in mid and late expiration advanced the onset of the next inspiration, shortening its duration. Stimulation in early inspiration advanced, while that in late inspiration delayed, the onset of the next expiration. These effects were often accompanied by changes in phrenic motoneuron firing patterns (earlier recruitment, increased discharge frequency, increased slope of integrated phrenic neurogram). Repetitive somatic afferent stimulation produced sustained increases in respiratory frequency in all cats and in half of them entrainment of respiratory frequency to the frequency of stimulation occurred at ratios such as 4:3, 4:5, 1:2, 1:3, 1:4, and 1:7. The lowest stimulus intensity required for evoking these phase shifts was between 5 and 10T (threshold of most excitable fibers) for muscle afferents and between 1 and 2T for cutaneous afferents. These results demonstrate the existence of a reflex mechanism capable of locking respiratory frequency to that of a periodic somatic afferent input. They also provide an experimental basis for the hypothesis that reflexes are resposible for the observed locking between step or pedal frequency and respiratory rate during exercise in man.     

Altered breathing pattern elicited by stimulation of abdominal visceral afferents

The effect of stimulation of afferent mesenteric nerves on tidal volume (VT), phrenic nerve, and external intercostal muscle activities was studied in anesthetized spontaneously breathing cats. Both mechanical distension of the small intestine and electrical stimulation of the mesenteric nerves resulted in an initial inspiratory inhibition of VT followed by a gradual recovery above the prestimulus controls. Changes in VT were accompanied by a depression of phrenic nerve activity and an excitation of external intercostal muscle activity. During the recovery phase of VT, the amplitude of phrenic nerve activity returned only partially, whereas the activity of the external intercostal muscle was greater than the prestimulus controls. In a second group of experiments, brief tetanic stimulation at the beginning of inspiration led to a complete and maintained inhibition of phrenic nerve activity but with a simultaneous excitation of external intercostal muscle activity and without any change in VT; whereas expiratory stimulation caused a decrease in expiratory abdominal muscle activity, without changing the peak amplitude of phrenic nerve activity. The respiratory changes observed with distension of the small intestine were abolished after denervation of the mesenteric plexus. It is concluded that activation of the visceral afferents of the mesenteric region reflexly changes diaphragmatic breathing to intercostal breathing. It is assumed that such a type of breathing pattern may occur in pregnancy and in pathophysiological situations involving splanchnic viscera.     

Analysis of entrainment of respiratory rhythm by somatic afferent stimulation in cats using phase response curves

To elucidate how peripheral somatic afferents synchronize the respiratory rhythm to the exercise rhythm, the phrenic nerve activity in the vagotomized, paralyzed, and artificially ventilated cats anesthetized with chloralose-urethane was recorded during electrical stimulation of the superficial radial nerve afferents. At first, a single pulse train was given at various times of the respiratory cycle to obtain a phase-response curve (PRC). The stimulation given at mid to late expiration produced a phase advance, but the stimulation during inspiration produced no measurable phase shifts in most animals (8/10). The maximum phase advance changed depending on the stimulus intensity. The stronger the stimulus intensity, the greater became the maximum phase advance. Repetitive somatic afferent stimulation produced 1:1 entrainment of the respiratory frequency to the repetitive stimulation. Theoretical predictions on the stable entrainment phase and on the entrainment frequency range from the obtained PRC were close to the experimental results. The present study demonstrated the presence of a neuronal circuit synchronizing the respiratory rhythm to the periodic somatic afferents and the manner of how such entrainment occurs.     

Respiratory modulation of the startle reflex in cats

Phase respiratory influences on reflex after-discharges in response to stimulation of the segmental nerves as well as tactile and acoustic stimulation in the limb and intercostal nerves — physiological analogs of startle reflexes (SR) were studied in unanesthetized (decerebrate) or chloralose-anesthetized cats. It was found that the level of these reflexes in the inhalation phase of respiration was 8–58% lower than during exhalation. The difference between the inhalation and exhalation phases was determined for different types of reflexes and under varying experimental conditions. Evidence was obtained that respiratory modulation of reflexes occurs mainly at the level of suprasegmental (reticular) mechanisms. Clear distinctions could be drawn between the pattern of reflex modulation in the lower intercostal nerves and those of the limbs. Findings would lead to the conclusion that the likely mechanisms underlying suprasegmental respiratory influences on these reflexes differ, as does the organization of their reticular centers.S. V. Kurashov Medical Institute, Ministry of Public Health of the RSFSR, Kazan'. Translated from Neirofiziologiya, Vol. 18, No. 5, pp. 593–603, September–October, 1986.     

Suppression of postsynaptic response in trigeminal motoneurons by stimulating the midbrain central gray matter

The effects of stimulating the midbrain central gray matter (CGM) on motoneuronal response in trigeminal nerves were investigated in anesthetized cat. It was found that stimulating the CGM did not induce postsynaptic response in these motoneurones. Conditioning stimulation of the CGM brought about suppression of motoneuronal postsynaptic response to stimulation of tooth pulp and high threshold infraorbital nerve afferents without affecting motoneuronal antidromic response and jaw-opening reflex as induced by stimulating the caudal nucleus of the spinal trigeminal tract. It was thus concluded that stimulating the CGM exerts no direct effect on motoneurons but does have an influence on postsynaptic response — a result of modulation of the afferent spike flow at interneuronal level.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 22, No. 4, pp. 543–549, July–August, 1990.     

Influences from laryngeal afferents on expiratory bulbospinal neurons and motoneurons

The purpose of this study is to analyze the reflex effects of laryngeal afferent activation on respiratory patterns in anesthetized, vagotomized, paralyzed, ventilated cats. We recorded simultaneously from the phrenic nerve, T10 internal intercostal nerve, and single bulbospinal expiratory neurons of the caudal ventral respiratory group (VRG). Laryngeal afferents were activated by electrical stimulation of the superior laryngeal nerve (SLN) or by cold-water infusion into the larynx. Both types of stimuli caused inhibition of phrenic activity and facilitation of internal intercostal nerve activity, indicating expiratory effort. The activity of 46 bulbospinal expiratory cells was depressed during SLN electrical stimulation, and 13 of them were completely inhibited. In 44 of 56 neurons tested, mean firing frequency (FFmean) was decreased in response to cold-water infusion and 8 others responded with increased FFmean; in the remaining 4 neurons, FFmean was unchanged. Possible reasons for different neuronal responses to SLN electrical stimulation and water infusion are discussed. We conclude that bulbospinal expiratory neurons of VRG were not the source of the reflex motoneuronal expiratory-like activity produced by SLN stimulation. Other, not yet identified inputs to spinal expiratory motoneurons are activated during this experimental condition.     

Respiratory rhythm generation in rats: The importance of inhibition

Stimulation-related modifications of activity in the phrenic nerve and external and internal intercostal nerves were studied on urethane-anesthetized rats; the inspiratory medullary structures were stimulated. The activity was recorded either following microinjections of gamma-aminobutyric acid (GABA) or its derivatives into the medial parabrachial nuclei and rostral part of the ventral respiratory group of medullary neurons, or without such microinjections. Gradual dependence of activity in these nerves on the phase of the respiratory cycle was established. It was shown that the higher was the integrated inspiratory activity, the lower became the relative gain in phrenic nerve activity caused by standard stimulation. When stimulation was applied at the postinspiratory phase, the threshold stimulus intensity showed an S-like rise with an increase in integrated inspiratory activity. Microinjections of GABA or its cyclic derivatives into the parabrachial nuclear structures decreased the inhibitory effects of the latter. During the postinspiratory phase, the effect was opposite: an increase in the relative gain of inspiratory activity and drop in the threshold. The resulting data suggest that there is a two-level organization of the respiratory regulatory inhibition and that the whole respiratory neuronal network has a compartmental structure.Neirofiziologiya/Neurophysiology, Vol. 25, No. 6, pp. 420–426, November–December, 1993.     

Stimulation of groups III and IV phrenic afferents reflexly decreases total lung resistance in dogs

Little is known about the reflex effect on airway caliber evoked by stimulation of phrenic afferents. Therefore, in chloralose-anesthetized, paralyzed dogs, we recorded airflow, airway pressure, arterial pressure, and heart rate while electrically stimulating a phrenic nerve. Total lung resistance was calculated breath by breath. The phrenic nerve was stimulated at 3, 5, 20, 70, 140, and 200 times motor threshold and the compound action potential was recorded. Stimulation of the phrenic nerve at three and five times threshold, which activated groups I, II, and a few group III fibers, had no effect on any of the variables measured. Stimulation at 20 times threshold, which activated many group III fibers and groups I and II fibers, reflexly decreased resistance. Stimulation at 70, 140, and 200 times threshold, which activated groups I-IV fibers, evoked progressively greater decreases in lung resistance. The reflex bronchodilation evoked by phrenic nerve stimulation was unaffected by propranolol or phentolamine but was abolished by atropine. We conclude that activation of groups III and IV phrenic nerve afferents reflexly decreased total lung resistance by withdrawing cholinergic tone to airway smooth muscle.     

Effects of stimulating the periaqueductal gray matter on high- and low-threshold startle reflexes

The effects of stimulating the periaqueductal gray matter (PAG) on two types of startle reflex (spino-bulbo-spinal reflex produced by intensive stimulation of the peripheral nerves and low-threshold tactile spino-reticulo-spinal reflex) as well as high-threshold jaw-opening reflex arising in response to tooth pulp stimulation were investigated in cats anesthetized with chloralose. Simulating most PAG test sites led to pronounced inhibition of jaw-opening reflex, profound depression of spino-bulbo-spinal reflex, and moderate inhibition of tactile reflexes. The facilitatory effect of stimulating a number of PAG sites on the latter reflexes was demonstrated. Effects of PAG stimulation fell into two classes: brief, measurable in hundreds of msec and more prolonged, measured in minutes and seconds. Findings would indicate certain differences between the effects of PAG stimulation low-threshold (non-nociceptive) and high-threshold (nociceptive) startle reflexes, of which the possible mechanisms are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 1, pp. 71–78, January–February, 1989.     

Synaptic processes in thoracic α-motoneurons evoked by segmental afferent stimulation

Synaptic processes in various functional groups of thoracic motoneurons (Th₉-Th₁₁) evoked by stimulation of segmental nerves were investigated in anesthetized and decerebrate cats. No reciprocal relations were found between these groups of motoneurons. Only excitatory mono- and polysynaptic responses were recorded in the motoneurons of the principal intercostal nerve following stimulation of the homonymous nerve. Activation of the afferents of the external intercostal muscle and dorsal branches does not cause noticeable synaptic processes in these motoneurons; much more rarely it is accompanied by the development of low-amplitude polysynaptic EPSP's. In motoneurons of the dorsal branches, stimulation of homonymous nerves leads to the appearance of simple, short-latent EPSP's. Late responses of the IPSP or EPSP - IPSP type with a predominance of the inhibitory component were observed in most motoneurons of this type following activation of the afferent fibers of the principal intercostal nerve. In other motoneurons of the dorsal muscles, stimulation of the main intercostal nerve (and nerve of the external intercostal muscle) did not evoke apparent synpatic processes. EPSP's (mono- and polysynaptic) appeared in the motoneurons of the external intercostal muscle following stimulation of the homonymous and main intercostal nerves. Activation of the afferents of the dorsal branches was ineffective. The character of the synaptic responses of the respiratory motoneurons to segmental afferent stimulation, investigated under conditions of spontaneous respiration, was different. The characteristics of synaptic activation of thoracic motoneurons by segmental afferents under conditions of hyperventilation apnea and during spontaneous breathing of the animals are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 2, No. 3, pp. 279–288, May–June, 1970.     

Comparative study of sympathetic and parasympathetic firing in automatic nerves produced by stimulating different structures of the cat hypothalamus

It was discovered by making simultaneous recordings of evoked hypothalamic-parasympathetic and hypothalamic-sympathetic firing that sympathetic discharges in the splanchnic nerve and parasympathetic discharges in the pelvic nerve with minimum latency and lowest threshold level could be obtained by stimulating the posterolateral hypothalamus. It was also found that the focus of maximum neuronal activity produced by stimulating afferent visceral nerve fibers as well as the highest concentration of evoked efferent response in sympathetic and parasympathetic nerves were located in the same hypothalamic area. A working hypothesis was put forward that convergent polysensory hypothalamic neurons also act as divergent polyeffector constituents of the integrative system of the hypothalamovisceral reflex arc.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 19, No. 4, pp. 482–491, July–August, 1987.     

Synaptic excitation of reticulospinal neurons during the startle reaction in cats anesthetized with chloralose

Synaptic processes in reticulospinal neurons of the pons and medulla during the startle reaction evoked by somatic stimulation were investigated in cats anesthetized with chloralose. The main type of response of reticulospinalneurons was found to be PSPs involving intrareticular (proprioreticular) pathways of varied complexity: oligosynaptic (including supposedly monosynaptic) and polysynaptic. Comparison of EPSP characteristics with parameters of spino-bulbospinal (SBS) discharges recorded simultaneously in the intercostal nerves showed that polysynaptic EPSPs evoked through corresponding proprioreticular pathways were most effective in creating a descending SBS volley. About half the reticulospinal neurons of the pons and medulla were involved at any one time in the synaptic relay process during the startle reflex. The conduction velocity in axons of these neurons varied from 30 to 98 m/sec (means 64.5 Mp 16.5 m/sec). Some distinguishing features of the functional organization of the reticular "center" for the startle reaction are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 13, No. 6, pp. 594–603, November–December, 1981.     

Respiratory responses in reversible diaphragm paralysis

The effects of diaphragm paralysis on respiratory activity were assessed in 13 anesthetized, spontaneously breathing dogs studied in the supine position. Transient diaphragmatic paralysis was induced by bilateral phrenic nerve cooling. Respiratory activity was assessed from measurements of ventilation and from the moving time averages of electrical activity recorded from the intercostal muscles and the central end of the fifth cervical root of the phrenic nerve. The degree of diaphragm paralysis was evaluated from changes in transdiaphragmatic pressure and reflected in rib cage and abdominal displacements. Animals were studied both before and after vagotomy breathing O2, 3.5% CO2 in O2, or 7% CO2 in O2. In dogs with intact vagi, both peak and rate of rise of phrenic and inspiratory intercostal electrical activity increased progressively as transdiaphragmatic pressure fell. Tidal volume decreased and breathing frequency increased as a result of a shortening in expiratory time. Inspiratory time and ventilation were unchanged by diaphragm paralysis. These findings were the same whether O2 or CO2 in O2 was breathed. After vagotomy, no significant change in phrenic or inspiratory intercostal activity occurred with diaphragm paralysis in spite of increased arterial CO2 partial pressure. Ventilation and tidal volume decreased significantly, and respiratory timing was unchanged. These results suggest that mechanisms mediated by the vagus nerves account for the compensatory increase in respiratory electrical activity during transient diaphragm paralysis. That inspiratory time is unchanged by diaphragm paralysis whereas the rate or rise of phrenic nerve activity increases suggest that reflexes other than the Hering-Breuer reflex contribute to the increased respiratory response.     

Attenuation of phrenic motor discharge by phrenic nerve afferents

Short latency phrenic motor responses to phrenic nerve stimulation were studied in anesthetized, paralyzed cats. Electrical stimulation (0.2 ms, 0.01-10 mA, 2 Hz) of the right C5 phrenic rootlet during inspiration consistently elicited a transient reduction in the phrenic motor discharge. This attenuation occurred bilaterally with an onset latency of 8-12 ms and a duration of 8-30 ms. Section of the ipsilateral C4-C6 dorsal roots abolished the response to stimulation, thereby confirming the involvement of phrenic nerve afferent activity. Stimulation of the left C5 phrenic rootlet or the right thoracic phrenic nerve usually elicited similar inhibitory responses. The difference in onset latency of responses to cervical vs. thoracic phrenic nerve stimulation indicates activation of group III afferents with a peripheral conduction velocity of approximately 10 m/s. A much shorter latency response (5 ms) was evoked ipsilaterally by thoracic phrenic nerve stimulation. Section of either the C5 or C6 dorsal root altered the ipsilateral response so that it resembled the longer latency contralateral response. The low-stimulus threshold and short latency for the ipsilateral response to thoracic phrenic nerve stimulation suggest that it involves larger diameter fibers. Decerebration, decerebellation, and transection of the dorsal columns at C2 do not abolish the inhibitory phrenic-to-phrenic reflex.     

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.     

Ventilatory effects of stimulation of phrenic afferents

The diaphragm, a ventilatory muscle, has abundant sensory innervation. The effects of phrenic afferent activation on ventilation have been varied. In this study the proximal end of the phrenic nerve was electrically stimulated, and the effects on ventilation were measured in supine dogs anesthetized with either alpha-chloralose or pentobarbital sodium. We found a maximum increase in ventilation of 45 +/- 4% in the alpha-chloralose group and an increase in mean arterial blood pressure of 18 +/- 4%. This response was obtained at high stimulus intensities (60 times twitch threshold). Stimulation of the proximal end of the gastrocnemius nerve produced a similar ventilatory response (61 +/- 10%) but at lower stimulus intensities. During pentobarbital sodium anesthesia both the hyperventilation and the pressor response were produced; however, ventilation was increased by an increase in respiratory frequency. The reflex was abolished by sectioning of the cervical dorsal roots (C4-C7). Proximal cold blockade of the nerve abolished the response at a perineural temperature of 1.35 +/- 0.64 degrees C. The main effect of activation of phrenic afferents was an increase in ventilation and blood pressure that was mediated by unmyelinated fibers and possibly thin myelinated fibers. This response is similar to skeletal muscle afferent activation and may play a role in ventilatory drive during such conditions as exercise and respiratory muscle fatigue.     

Expiratory neural activities in gasping

The purpose was to characterize expiratory-related neural activities in eupnea and gasping. In decerebrate and vagotomized cats, activities were recorded from the phrenic nerve, spinal intercostal and abdominal nerves, and recurrent laryngeal nerve and its branches. Neural inspiration was defined by phrenic discharge. The spinal and laryngeal nerves discharged in inspiration, expiration, or during both phases. Gasping was induced by freezing the brain stem at the pontomedullary junction, exposure to asphyxia or anoxia, or ligation of the basilar artery and its branches. In gasping, peak phrenic activity typically increased as did inspiratory-related activities of laryngeal and spinal nerves. Expiratory activities were greatly reduced in gasping, with some activities being completely eliminated. Reductions of expiratory activity were more prominent for spinal than laryngeal nerves. Similar results were obtained in cats having intact vagi that were ventilated with a servo-respirator so that lung inflation paralleled phrenic activity. The concept that gasping differs fundamentally form other ventilatory patterns is discussed.     

Effects of stimulating midbrain central gray matter on neuronal response in the caudal trigeminal nucleus to peripheral nerve stimulation

Stimulating the midbrain central gray matter (CGM) with trains of 10–20 stimuli was found to inhibit response to electrical stimulation of infraorbital nerve and tooth pulp A-alpha and A-delta afferents at 100 msec intervals in 65% of the caudal trigeminal nucleus in neurons tested during experiments on cats under chloralose-Nembutal anesthesia. Response was inhibited most effectively in convergent neurons (activated by stimulating infraorbital nerve and tooth pulp A-alpha and A-delta afferents) to stimulating tooth pulp (0.76) and, to a somewhat lesser degree, to stimulation of A-alpha afferents (0.6). For high-threshold neurons (activated by stimulating infraorbital nerve and tooth pulp A-delta afferents), success rate of inhibiting response under the effects of CGM stimulating measured 0.71 and 0.48 for low-threshold cells (activated by stimulating infraorbital nerve A-alpha afferents). Stimulating CGM produced an excitatory response in 10 caudal trigeminal nucleus neurons within 7.5–20 msec; after this neurons showed no reaction to peripheral nerve stimulation for a 200–450 msec period. The possible involvement of these neurons in pressing the mouth-opening reflex produced by CGM stimulation is discussed in this article.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 20, No. 6, pp. 729–736, November-December, 1988.     

A technique for recording from intact phrenic nerve afferents

Recent evidence has suggested that phrenic nerve afferents can influence respiratory motor drive. This paper presents a technique whereby the activity of single phrenic nerve afferents can be recorded from uncut dorsal root filaments. Cervical dorsal roots 4, 5, and 6 were exposed by dorsal laminectomy in 10 anesthetized, spontaneously breathing cats. A stimulating electrode was placed on the right whole phrenic nerve low in the neck. The animal was then placed in a spinal suspension frame. Dissection of the dorsal root filaments was performed with probes made of fine tungsten wire. Single filaments were isolated intact from the dorsal root fascicles and placed across a tungsten electrode. Fiber classification was performed by determining conduction velocity. Monopolar recordings were made from a total of 38 fibers. Tonic activity was observed in 21, respiratory-related activity was evident in 15, and two fibers were silent but could be recruited by phrenic nerve stimulation. The conduction velocities ranged from 2.2 to 103 m/s. Approximately one-half of the fibers had conduction velocities of less than 20 m/s. This technique offers a way to record the activity of diaphragm afferents while maintaining the integrity of possible reflex pathways. Application of this method should prove helpful in elucidating the possible role of the various diaphragm afferents in the control of respiratory motor drive.     

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.