Expiratory Pattern Research Articles

Breathing-swallow dysfunction in COPD: How silent aspiration may be contributing to exacerbations.

Breathing-swallow dysfunction in COPD: How silent aspiration may be contributing to exacerbations.

Inhibitory control of active expiration by the Bötzinger complex in rats.

Contraction of abdominal muscles at the end of expiration during metabolic challenges (such as hypercapnia and hypoxia) improves pulmonary ventilation. The emergence of this active expiratory pattern requires the recruitment of the expiratory oscillator located on the ventral surface of the medulla oblongata. Here we show that an inhibitory circuitry located in the Bötzinger complex is an important source of inhibitory drive to the expiratory oscillator. This circuitry, mediated by GABAergic and glycinergic synapses, provides expiratory inhibition that restrains the expiratory oscillator under resting condition and regulates the formation of abdominal expiratory activity during active expiration. By combining experimental and modelling approaches, we propose the organization and connections within the respiratory network that control the changes in the breathing pattern associated with elevated metabolic demand. The expiratory neurons of the Bötzinger complex (BötC) provide inhibitory inputs to the respiratory network, which, during eupnoea, are critically important for respiratory phase transition and duration control. Here, we investigated how the BötC neurons interact with the expiratory oscillator located in the parafacial respiratory group (pFRG) and control the abdominal activity during active expiration. Using the decerebrated, arterially perfused in situ preparations of juvenile rats, we recorded the activity of expiratory neurons and performed pharmacological manipulations of the BötC and pFRG during hypercapnia or after the exposure to short-term sustained hypoxia - conditions that generate active expiration. The experimental data were integrated in a mathematical model to gain new insights into the inhibitory connectome within the respiratory central pattern generator. Our results indicate that the BötC neurons may establish mutual connections with the pFRG, providing expiratory inhibition during the first stage of expiration and receiving excitatory inputs during late expiration. Moreover, we found that application of GABAergic and glycinergic antagonists in the BötC caused opposing effects on abdominal expiratory activity, suggesting complex inhibitory circuitry within the BötC. Using mathematical modelling, we propose that the BötC network organization and its interactions with the pFRG restrain abdominal activity under resting conditions and contribute to abdominal expiratory pattern formation during active expiration observed during hypercapnia or after the exposure to short-term sustained hypoxia.

Respiratory-Swallow Pattern Following Total Laryngectomy.

The goal of this study was to further characterize respiratory patterns in total laryngectomees with attention to respiratory-swallow pattern as it relates to presence/absence of tracheoesophageal puncture (TEP) and bolus consistency. It was hypothesized that participants with TEP would exhibit respiratory-swallow patterns that were significantly different than those without TEP and that bolus consistency (thin or solid) would modulate respiratory-swallow pattern. Data were collected from 12 adults (8 male), aged 46-67years (mean 57) status post total laryngectomy (1-30years; average 6years). Those actively receiving chemoradiation, with history of esophageal cancer, with neurologic disease, with history of lung cancer, with known or suspected recurrence of head and neck cancer (HNC), or with severe cognitive deficits were excluded. Laryngectomy participants were asked to swallow three sips of water and three bites of graham cracker. Submental surface EMG activity was used to detect swallows and a custom stoma mask in line with a pneumotachograph measured airflow during the swallows. Non-parametric Mann-Whitney test for differences was used to detect significance for our dependent variables, TEP or bolus consistency and independent variables, respiratory-swallow pattern. Laryngectomee's showed preference for swallow during inspiration which is inconsistent with the expiratory pattern preference found in healthy adults with intact larynges by McFarland et al. (Respir Physiol Neurobiol 234:89-96, 2016) but consistent with the pattern preference for inspiration (or non-dominant respiratory-swallow phase pattern) found in the HNC population at-large by Brodsky et al. (J Appl Physiol 112(10):1698-1705, 2012). No significant difference was found in swallow pattern with regards to presence/absence of TEP or bolus consistency.

High‐flow nasal therapy – modelling the mechanism

High‐flow nasal therapy – modelling the mechanism

Assessment of impaired coordination between respiration and deglutition in children and young adults with ataxia telangiectasia.

This cross-sectional investigation aimed to assess the value of non-invasive measures of temporal respiratory-swallow coupling in individuals with ataxic swallowing. Twenty participants (11 males, 9 females; range 9-21y) with ataxia telangiectasia were presented with water and pudding boluses. Their 193 swallows were compared with 2200 swallows from 82 age-matched healthy controls. The two components of airway protection during swallowing that were analyzed were: direction of peri-deglutitive airflow and duration of deglutitive inhibition of respiratory airflow (DIORA). Safe expiratory patterns of peri-deglutitive airflow occurred significantly less often in participants with ataxia telangiectasia than in age-matched control participants (younger p<0.015 and older p<0.001). The frequency of an expiratory pattern of peri-deglutitive airflow increased with age in participants in the comparison group (p=0.006), but not in those with ataxia telangiectasia (p=0.234). With age, mean duration of DIORA decreased in controls (p<0.001) but was unchanged in participants with ataxia telangiectasia (p=0.164). Non-invasive quantitative measures of respiratory-swallow coupling capture temporal relationships that plausibly contribute to airway compromise from dysphagia. Changes in respiratory-swallow coupling observed with advancing age in control participants were not seen in participants with ataxia telangiectasia. Measures of perturbations may herald swallowing problems prior to development of pulmonary and nutritional sequelae.

Long-term facilitation of expiratory and sympathetic activities following acute intermittent hypoxia in rats.

Acute intermittent hypoxia (AIH) promotes persistent increases in ventilation and sympathetic activity, referred as long-term facilitation (LTF). Augmented inspiratory activity is suggested as a major component of respiratory LTF. In this study, we hypothesized that AIH also elicits a sustained increase in expiratory motor activity. We also investigated whether the expiratory LTF contributes to the development of sympathetic LTF after AIH. Rats were exposed to AIH (10×6-7% O2 for 45s, every 5min), and the cardiorespiratory parameters were evaluated during 60min using invivo and insitu approaches. In unanesthetized conditions (n=9), AIH elicited a modest but sustained increase in baseline mean arterial pressure (MAP, 104±2 vs. 111±3mmHg, P<0.05) associated with enhanced sympathetic and respiratory-related variabilities. In the insitu preparations (n=9), AIH evoked LTF in phrenic (33±12%), thoracic sympathetic (75±25%) and abdominal nerve activities (69±14%). The sympathetic overactivity after AIH was phase-locked with the emergence of bursts in abdominal activity during the late-expiratory phase. In anesthetized vagus-intact animals, AIH increased baseline MAP (113±3 vs. 122±2mmHg, P<0.05) and abdominal muscle activity (535±94%), which were eliminated after pharmacological inhibition of the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG). These findings indicate that increased expiratory activity is also an important component of AIH-elicited respiratory LTF. Moreover, the development of sympathetic LTF after AIH is linked to the emergence of active expiratory pattern and depends on the integrity of the neurones of the RTN/pFRG.

Serotoninergic Antagonism in the Retrotrapezoid Nucleus Prevents the Expiratory Long‐Term Facilitation Induced by Acute Intermittent Hypoxia

Serotonin (5‐HT) plays an important role in the development of sympathetic and phrenic long‐term facilitation (LTF) elicited by acute intermittent hypoxia (AIH). Herein, we evaluated the role of 5‐HT in the retrotrapezoid nucleus (RTN) on the emergence of active expiratory pattern in response to AIH. Using anesthetized (urethane; 1.2 g/Kg, ip) male Holztmann rats (280‐290 g), we analyzed the changes in the arterial pressure, heart rate and in the diaphragmatic and abdominal (ABD) activities elicited by single and repeated (3 times, 5 min apart) bilateral microinjections of 5‐HT (1mM, 50nl) in the RTN. We also analyzed the effects of bilateral microinjections of ketanserin (5‐HT2A antagonist; 10 µM, 50 nl) in the RTN on the cardiorespiratory changes induced by AIH (10 times of 6‐7% O2, for 45 s, each 5 min). Repeated, but not single, microinjections of 5‐HT in the RTN (n=7) elicited a sustained increase in the abdominal expiratory activity (ΔABD: 85±33%, 60 min after microinjections, P&lt;0.05) that was prevented by previous microinjections of ketanserin. The 5HT2A receptor antagonism in the RTN during AIH exposure also prevented the increase in ABD activity evoked by AIH (ΔEMGABD: 40±9 vs ‐1±1% 60 min after AIH, respectively vehicle and ketanserin; P&lt;0.05). The other cardiorespiratory parameters were not affected by the 5‐HT and the ketanserin microinjections in the RTN. Our results indicate that, in anesthetized conditions, the activation of serotoninergic receptors in the RTN is sufficient to promote a sustained increase in abdominal activity and required for the emergence of expiratory LTF induced by AIH. Supported by FAPESP, CNPq, CAPES and PROPe.

Short‐term sustained hypoxia induces changes in the coupling of sympathetic and respiratory activities in rats

Individuals experiencing sustained hypoxia (SH) exhibit adjustments in the respiratory and autonomic functions by neural mechanisms not yet elucidated. In the present study we evaluated the central mechanisms underpinning the SH-induced changes in the respiratory pattern and their impact on the sympathetic outflow. Using a decerebrated arterially perfused in situ preparation, we verified that juvenile rats exposed to SH (10% O2) for 24h presented an active expiratory pattern, with increased abdominal, hypoglossal and vagal activities during late-expiration (late-E). SH also enhanced the activity of augmenting-expiratory neurones and depressed the activity of post-inspiratory neurones of the Bötzinger complex (BötC) by mechanisms not related to changes in their intrinsic electrophysiological properties. SH rats exhibited high thoracic sympathetic activity and arterial pressure levels associated with an augmented firing frequency of pre-sympathetic neurones of the rostral ventrolateral medulla (RVLM) during the late-E phase. The antagonism of ionotropic glutamatergic receptors in the BötC/RVLM abolished the late-E bursts in expiratory and sympathetic outputs of SH rats, indicating that glutamatergic inputs to the BötC/RVLM are essential for the changes in the expiratory and sympathetic coupling observed in SH rats. We also observed that the usually silent late-E neurones of the retrotrapezoid nucleus/parafacial respiratory group became active in SH rats, suggesting that this neuronal population may provide the excitatory drive essential to the emergence of active expiration and sympathetic overactivity. We conclude that short-term SH induces the activation of medullary expiratory neurones, which affects the pattern of expiratory motor activity and its coupling with sympathetic activity.

Central respiratory and sympathetic adaptations induced by sustained hypoxia

Individuals experiencing high altitudes frequently exhibited respiratory and autonomic adjustments as a consequence of the exposure to sustained hypoxia (SH). However, the responses to SH may be inappropriate and cause serious ventilatory and circulatory maladaptations. We have been exploring the central mechanisms underlying the cardiorespiratory adjustments to SH. Using the decerebrated arterially-perfused in situ preparations of rats, we verified that SH exposure (10% O2 for 24h) transforms the expiratory pattern into an active process, with the emergence of additional bursts in the abdominal motor activity during late-expiration (late-E).

Active expiration and sympathetic overactivity induced by short‐term sustained hypoxia in rats

Short‐term sustained hypoxia (SH, 24 hrs) produces changes in the respiratory motor activity. However, the neurochemical and electrophysiological basis of these changes are poorly understood. In the present study, we evaluated the central mechanisms underlying the respiratory changes induced by SH (10% O2) and the correlated changes in sympathetic activity. Using arterially‐perfused in situ preparations, we observed that SH rats (n=20), but not controls, exhibited late‐expiratory (late‐E) bursts in abdominal nerve (P&lt;0.05) associated with depressed post‐inspiratory and increased augmenting‐expiratory activities of neurons in the Bötzinger complex (BötC, P&lt;0.05). SH rats also exhibited additional late‐E bursts in thoracic sympathetic activity associated with larger Traube‐Hering wave amplitudes (P&lt;0.05). Corroborating these findings, we observed in unanesthetized rats that the arterial pressure levels of SH rats (n=7) exhibited augmented low‐and high‐frequency variabilities (P&lt;0.05). Besides, the antagonism of ionotropic glutamate receptors in the BötC eliminated the late‐E activity in respiratory and sympathetic nerves. Our data indicate that short‐term SH alters the expiratory pattern and its coupling with sympathetic nervous system by mechanisms involving changes of neuronal activities and glutamatergic transmission in the BötC.

Proof of concept: differential effects of Valsalva and straining maneuvers on the pelvic floor

To prove a basic physiological principle in healthy women, demonstrating different movement patterns of diaphragm, pelvic floor, and muscular wall surrounding the abdominal cavity during a Valsalva maneuver as opposed to a straining maneuver, by means of real-time dynamic magnetic resonance imaging (MRI). The study was performed at Hochzirl Hospital, Austria and Department of Radiology, Medical University Innsbruck, Austria. Four healthy women underwent MRI measurements in a 1.5-T whole body MR-scanner. Coronal, sagittal, and axial slices were acquired simultaneously and a dynamic MRI sequence was used to assess cranio-caudal movements of the diaphragm and pelvic floor and of concomitant changes in anterolateral abdominal muscle thickness and abdominal diameter at the umbilical level. Both the Valsalva maneuver and the straining maneuver began with deep inspiration and downward movement of the diaphragm. During the exertion phase of both maneuvers, abdominal muscle thickness increased and abdominal diameter decreased. During the Valsalva maneuver, the pelvic floor moved cranially parallel to the diaphragm, whereas during the straining maneuver, the pelvic floor was markedly displaced caudally. The Valsalva maneuver reflects an expiratory pattern with diaphragm and pelvic floor elevation, whereas during straining the pelvic floor descends.

Sympathetic overactivity coupled with active expiration in rats submitted to chronic intermittent hypoxia

It is well known that the respiration modulates sympathetic outflow in basal conditions. Recordings of sympathetic nerve activity demonstrated that central respiratory activity produces rhythmical oscillations in sympathetic discharge that appear mainly during inspiratory phase. This led us to hypothesize that changes in the mechanisms regulating the central entrainment between respiratory and sympathetic activities may contribute to sympathetic overactivity and hypertension. This issue was addressed using rats submitted to chronic intermittent hypoxia (CIH), in which we evaluated whether or not the sympathetic overactivity and hypertension observed in these animals were linked to changes in respiratory pattern. We verified that under baseline conditions, CIH rats exhibited a reduction in post-inspiratory activity of vagus nerve and an enhanced late-expiratory activity in abdominal motor nerve. As a consequence of this altered expiratory pattern, we observed that CIH rats showed an additional burst in sympathetic activity phase-locked with the enhanced late-E expiratory activity. These findings pointed out that the entrainment between pontine-medullary expiratory and sympathetic neurons of CIH rats is strengthened, indicating for the first time in this experimental model that changes in the coupling of respiratory and sympathetic activities may contribute to hypertension. Subsequent studies performed in other models of hypertension also demonstrated similar changes, supporting the concept that alterations in central mechanisms of respiratory-sympathetic coupling is a novel and important mechanism to be considered in the pathogenesis of hypertension.

Structural and functional architecture of respiratory networks in the mammalian brainstem

Neural circuits controlling breathing in mammals are organized within serially arrayed and functionally interacting brainstem compartments extending from the pons to the lower medulla. The core circuit components that constitute the neural machinery for generating respiratory rhythm and shaping inspiratory and expiratory motor patterns are distributed among three adjacent structural compartments in the ventrolateral medulla: the Bötzinger complex (BötC), pre-Bötzinger complex (pre-BötC) and rostral ventral respiratory group (rVRG). The respiratory rhythm and inspiratory-expiratory patterns emerge from dynamic interactions between: (i) excitatory neuron populations in the pre-BötC and rVRG active during inspiration that form inspiratory motor output; (ii) inhibitory neuron populations in the pre-BötC that provide inspiratory inhibition within the network; and (iii) inhibitory populations in the BötC active during expiration that generate expiratory inhibition. Network interactions within these compartments along with intrinsic rhythmogenic properties of pre-BötC neurons form a hierarchy of multiple oscillatory mechanisms. The functional expression of these mechanisms is controlled by multiple drives from more rostral brainstem components, including the retrotrapezoid nucleus and pons, which regulate the dynamic behaviour of the core circuitry. The emerging view is that the brainstem respiratory network has rhythmogenic capabilities at multiple hierarchical levels, which allows flexible, state-dependent expression of different rhythmogenic mechanisms under different physiological and metabolic conditions and enables a wide repertoire of respiratory behaviours.

Multiple Rhythmic States in a Model of the Respiratory Central Pattern Generator

The three-phase respiratory pattern observed during normal breathing changes with alterations in metabolic or physiological conditions. A recent study using in situ perfused rat brain preparations demonstrated a reorganization of the respiratory pattern with sequential reduction of the brain stem respiratory network. Specifically, with removal of the pons, the normal three-phase pattern transformed to a two-phase inspiratory-expiratory pattern and, with more caudal transections, to one-phase, intrinsically generated inspiratory oscillations. A minimal neural network proposed to reproduce these transformations includes 1) a ringlike mutually inhibitory network composed of the postinspiratory, augmenting expiratory, and early-inspiratory neurons and 2) an excitatory preinspiratory neuron, with persistent sodium current (I(NaP))-dependent intrinsic bursting properties, that dynamically participates in the expiratory-inspiratory phase transition and inspiratory phase generation. We used activity-based single-neuron models and applied numerical simulations, bifurcation methods, and fast-slow decomposition to describe the behavior of this network in the functional states corresponding to the three-, two-, and one-phase oscillatory regimes, as well as to analyze the transitions between states and between respiratory phases within each state. We demonstrate that, although I(NaP) is not necessary for the generation of three- and two-phase oscillations, it contributes to control of the oscillation period in each state. We also show that the transitions between states can be produced by progressive changes of drives to particular neurons and proceed through intermediate regimes, featuring high-amplitude late-expiratory and biphasic-expiratory activities or ectopic burst generation. Our results provide important insights for understanding the state-dependent mechanisms for respiratory rhythm generation and control.

Spontaneous Breathing Patterns of Very Preterm Infants Treated With Continuous Positive Airway Pressure at Birth

There are no data describing how very preterm infants breathe spontaneously immediately after birth. We studied a convenience sample of spontaneously breathing infants <or=32 wk' gestation treated with facemask continuous positive airway pressure at birth. Airway pressure and flow were measured and each breath analyzed. Twelve infants had 792 breaths suitable for analysis. Results are given as mean (SD). Gestational age and birth weight were 29 (1.9) wk and 1220 (412) g. Recordings were started 159 (77) s after birth. The inspiratory pattern and duration was similar in all breaths at 0.36 (0.11) s. There were five expiratory patterns; most infants had more than one. In 79% of breaths expiratory duration (1.6 (1.1) s) was slowed or held by interruption or braking of expiratory flow. It was braked in 47% to a complete expiratory hold, in 22% by grunting or crying, and in 10% by slow or interrupted expiration. In 21% of the breaths, expiration was not interrupted and lasted 0.53 (0.13) s. Half of these breaths represented a panting pattern (rate >60 /min). Immediately after birth, most very preterm infants, treated with continuous positive airway pressure, frequently prolong their expiration by braking the expiratory flow. :

832 実形状肺気道モデルを用いた呼吸解析 : 呼気と吸気の比較(J05-3 生命体統合シミュレーション(3),ジョイントセッション,21世紀地球環境革命の機械工学:人・マイクロナノ・エネルギー・環境)

832 実形状肺気道モデルを用いた呼吸解析 : 呼気と吸気の比較(J05-3 生命体統合シミュレーション(3),ジョイントセッション,21世紀地球環境革命の機械工学:人・マイクロナノ・エネルギー・環境)

Distribution and medullary projection of respiratory neurons in the dorsolateral pons of the rat

The dorsolateral pons around the parabrachial nucleus including the Kölliker-Fuse nucleus is closely linked with the medullary respiratory center and plays an important role in respiratory control. We aimed to elucidate the firing properties, detailed distributions, and medullary projections of pontine respiratory neurons in pentobarbitone-anesthetized, paralyzed, and artificially ventilated rats with intact vagi. A total of 235 respiratory neurons were recorded from the dorsolateral pons in and around the Kölliker-Fuse nucleus. Six types of firing patterns were identified: inspiratory, expiratory–inspiratory phase spanning, inspiratory–expiratory phase spanning, decrementing expiratory, augmenting expiratory, and whole-phase expiratory patterns. Of these, the inspiratory neurons and the expiratory–inspiratory phase spanning neurons, which constituted the largest population (61%), were characterized most carefully by changing lung inflation levels, since under some conditions both showed similar firing patterns. Many (58%) of the 133 respiratory neurons examined were antidromically activated by electrical stimulation of the medulla. They were activated from the ventrolateral medulla around the ventral respiratory group and the Bötzinger complex and from the dorsomedial medulla around the nucleus tractus solitarii and the hypoglossal nucleus. The projections to the dorsomedial medulla were bilateral in many cases, and those to the ventrolateral medulla were unilateral. Of these medullary projections, two specific projections could be characterized in detail. First, many expiratory–inspiratory phase spanning neurons projected to the hypoglossal nucleus, suggesting that these pontine neurons are important premotor neurons of the hypoglossal motoneurons. This projection explains well the hypoglossal inspiratory activity, which is often dissociated from the phrenic inspiratory activity. Second, most whole-phase expiratory neurons that were distributed medially to the KF nucleus sent their axons toward the spinal cord via the midline medulla. These findings provide a new insight into the pontine control of medullary and spinal respiratory function.

Respiratory-modulated neuronal activities of the rostral medulla which may generate gasping.

Different neurophysiological mechanisms have been proposed to generate eupnea and gasping. Gasping is generated by neuronal mechanisms intrinsic to the medulla whereas a ponto-medullary neuronal circuit has been hypothesized to generate eupnea. Hence, neurons in the rostral medullary region which are critical for the neurogenesis of gasping are hypothesized to discharge differently in eupnea and gasping. In a perfused in situ preparation of the juvenile rat, these rostral medullary neuronal activities had inspiratory, expiratory and phase-spanning patterns in eupnea. In gasping, most expiratory and phase-spanning activities ceased, whereas many inspiratory neuronal activities changed to a decrementing pattern as that of the phrenic nerve. A limited proportion of neuronal activities acquired a 'pre-inspiratory' discharge in gasping. These neuronal activities, which were inspiratory or phase-spanning in eupnea, commenced discharge in neural expiration. This discharge peaked at the onset of the gasp and then decremented during neural inspiration. We hypothesize that these 'pre-inspiratory' neuronal activities generate the gasp by intrinsic pacemaker mechanisms.

Dissociation between respiratory effort and dyspnoea in a subset of patients with stroke.

Dyspnoea is not a prominent complaint of resting patients with recent hemispheric stroke (RHS). We hypothesized that, in patients with RHS presenting abnormalities in respiratory mechanics, increased respiratory motor output could translate into an increased perception of dyspnoea. We studied eight wheelchair-bound patients with RHS (mean age 62.4 years), previously evaluated by computerized tomography scanning, and a control group of normal subjects, matched for age and sex. We assessed routine spirometry, inspiratory and expiratory muscle pressures, breathing pattern and dyspnoea using a modified Borg scale. In six patients, we also measured oesophageal pressure during the maximal sniff manoeuvre and tidal inspiratory swing, and mechanical characteristics of the lung in terms of dynamic elastance during both quiet breathing and a hypercapnic/hyperoxic rebreathing test. During room air breathing, ventilation and tidal volume were similar in patients and controls, while tidal inspiratory swings of oesophageal pressure, an index of inspiratory motor output, were greater in patients ( P =0.005). Patients also exhibited a greater dynamic elastance ( P =0.013). During rebreathing, dynamic elastance remained higher ( P =0.01) and a greater than normal inspiratory motor output was found ( P =0.03). Responses of ventilation and tidal volume to carbon dioxide tension were normal, and in all patients but one a lower Borg score for the unit change in carbon dioxide tension and ventilation was found. In conclusion, a higher than normal inspiratory motor output was unexpectedly associated with a blunted perception of dyspnoea in this subset of RHS patients. This is likely to be due to the modulation of the integration process of respiratory sensation.

Phasic Vagal Sensory Feedback Transforms Respiratory Neuron ActivityIn Vitro

The isolated neonatal rat medulla generates respiratory-related rhythms recorded from cervical spinal cord ventral roots. When lungs and their vagal innervation are retained, respiratory activity is modulated by lung mechanoreceptor feedback: transient lung inflation triggered off inspiratory onset (phasic inflation) shortens inspiration and increases respiratory frequency. In this study, the activity of six respiratory neuron classes before and during phasic inflation was studied. Type 1 and 2 inspiratory neurons, identified in the transverse slice, were distinguished by the presence of a transient outward current or a hyperpolarization-activated inward current, respectively. Cell types only identified in the en bloc medulla included type II and III inspiratory neurons, distinguished by delayed onset and peri-inspiratory inhibition, respectively, and preinspiratory neurons, active before and after but silent during inspiration. Biphasic neurons, identified in the preparation used here, fired briskly during lung inflation but are otherwise quiescent. During phasic inflation, biphasic neurons showed a decrementing expiratory pattern of activity, matched by augmented postinspiratory hyperpolarization in type 1 neurons only, suggesting that biphasic neurons inhibit type 1 neurons, removing drive to other inspiratory neurons and terminating the inspiratory burst. This mechanism could account for a phasic inflation-induced increase in respiratory frequency via resetting effects. Alternatively, the phasic inflation-induced respiratory frequency increase may be attributable to slow facilitation. Slow modulation consistent with facilitation was apparent in the earlier onset of pre-I firing before inspiration and loss of postinspiratory firing and in the earlier onset of depolarization in type 2 neurons. On the basis of relative onset times and responses to phasic inflation, connectivity between these cell types is proposed.