Synaptic interactions between respiratory neurons during inspiratory on-switching evoked by vagal stimulation in decerebrate cats

To elucidate neuronal mechanisms underlying phase-switching from expiration to inspiration, or inspiratory on-switching (IonS), postsynaptic potentials (PSPs) of bulbar respiratory neurons together with phrenic nerve discharges were recorded during IonS evoked by vagal stimulation in decerebrate and vagotomized cats. A single shock stimulation of the vagus nerve applied at late-expiration developed an inspiratory discharge in the phrenic neurogram after a latency of 79+/-11 ms (n = 11). Preceding this evoked inspiratory discharge, a triphasic response was induced, consisting of an early silence (phase 1 silence), a transient burst discharge (phase 2 discharge) and a late pause (phase 3 pause). During phase 1 silence, IPSPs occurred in augmenting inspiratory (aug-I) and expiratory (E2) neurons, and EPSPs in postinspiratory (PI) neurons. During phase 2 discharge, EPSPs arose in aug-I neurons and IPSPs in PI and E2 neurons. These initial biphasic PSPs were comparable with those during inspiratory off-switching evoked by the same stimulation applied at late-inspiration. In both on- and off-switching, phase-transition in respiratory neuronal activities started to arise concomitantly with the phrenic phase 3 pause. These results suggest that vagal inputs initially produce a non-specific, biphasic response in bulbar respiratory neurons, which consecutively activates a more specific process connected to IonS.     

Synaptic origin of the respiratory-modulated activity of laryngeal motoneurons

To determine the synaptic source of the respiratory-related activity of laryngeal motoneurons, spike-triggered averaging of the membrane potentials of laryngeal motoneurons was conducted using spikes of respiratory neurons located between the Bötzinger complex and the rostral ventral respiratory group as triggers in decerebrate, paralyzed cats. We identified one excitatory and two inhibitory sources for inspiratory laryngeal motoneurons, and two inhibitory sources for expiratory laryngeal motoneurons. In inspiratory laryngeal motoneurons, monosynaptic excitatory postsynaptic potentials were evoked by spikes of inspiratory neurons with augmenting firing patterns, and monosynaptic inhibitory postsynaptic potentials (IPSPs) were evoked by spikes of expiratory neurons with decrementing firing patterns and by spikes of inspiratory neurons with decrementing firing patterns. In expiratory laryngeal motoneurons, monosynaptic IPSPs were evoked by spikes of inspiratory neurons with decrementing firing patterns and by spikes of expiratory neurons with augmenting firing patterns. We conclude that various synaptic inputs from respiratory neurons contribute to shaping the respiratory-related trajectory of membrane potential of laryngeal motoneurons.     

Studies on the synaptic interconnection between bulbar respiratory neurones of cats

In cats anaesthetized with pentobarbital, medullary respiratory neurones of both dorsal and ventral populations were recorded intracellularly with 1 mol·l^–1 KCl-electrodes. The neurones were classified according to the projection of their axons to the spinal cord (bulbospinal neurones) or to the vagal nerves (vagal neurones). Those neurones which could not be activated antidromically (NAA-neurones) by either procedure were subdivided into (inspiratory) R-neurones, which were monosynaptically excited by lung stretch receptor afferents, and into inspiratory and expiratory NAA-neurones, which did not receive a direct synaptic input, from these afferents.All types of neurone investigated revealed postsynaptic activity during both inspiration and expiration. The periods when synaptic activity was minimal were the periods of transition between respiratory phases.The input resistance of most respiratory neurones varied in parallel with the respiratory cycle. A drastic fall of the input resistance during expiration was observed in R-neurones and in some inspiratory vagal neurones. This was not seen in inspiratory bulbospinal neurones.In stable intracellular recordings, periodic postsynaptic inhibition was demonstrated in 52 of 53 respiratory neurones by IPSP reversal following chloride injection. Maximal membrane potential then was generally reached during one of the periods of respiratory phase transition. Reasons for the failure of others to demonstrate these IPSPs are presented and discrepancies between other findings and these are discussed. It is concluded that reciprocal inhibition between bulbar respiratory neurones does exist and is a general phenomenon.It is argued that reciprocal inhibition is the fundamental mechanism underlying respiratory gating of afferent inputs.The probable existence of recurrent inhibition is inferred from the changes in the pattern of membrane depolarization during the active period of neurones.Supported by the Deutsche Forschungsgemeinschaft     

Physiological properties of late inspiratory neurons and their possible involvement in inspiratory off-switching in cats

To assess the functional significance of late inspiratory (late-I) neurons in inspiratory off-switching (IOS), membrane potential and discharge properties were examined in vagotomized, decerebrate cats. During spontaneous IOS, late-I neurons displayed large membrane depolarization and associated discharge of action potentials that started in late inspiration, peaked at the end of inspiration, and ended during postinspiration. Depolarization was decreased by iontophoresis of dizocilpine and eliminated by tetrodotoxin. Stimulation of the vagus nerve or the nucleus parabrachialis medialis (NPBM) also evoked depolarization of late-I neurons and IOS. Waves of spontaneous chloride-dependent inhibitory postsynaptic potentials (IPSPs) preceded membrane depolarization during early inspiration and followed during postinspiration and stage 2 expiration of the respiratory cycle. Iontophoresed bicuculline depressed the IPSPs. Intravenous dizocilpine caused a greatly prolonged inspiratory discharge of the phrenic nerve (apneusis) and suppressed late-inspiratory depolarization as well as early-inspiratory IPSPs, resulting in a small constant depolarization throughout the apneusis. NPBM or vagal stimulation after dizocilpine produced small, stimulus-locked excitatory postsynaptic potentials (EPSPs) in late-I neurons. Neurobiotin-labeled late-I neurons revealed immunoreactivity for glutamic acid decarboxylase as well as N-methyl-D-aspartate (NMDA) receptors. These results suggest that late-I neurons are GABAergic inhibitory neurons, while the effects of bicuculline and dizocilpine indicate that they receive periodic waves of GABAergic IPSPs and glutamatergic EPSPs. The data lead to the conclusion that late-I neurons play an important inhibitory role in IOS. NMDA receptors are assumed to augment and/or synchronize late-inspiratory depolarization and discharge of late-I neurons, leading to GABA release and consequently off-switching of bulbar inspiratory neurons and phrenic motoneurons.     

Intracellular recordings from different types of medullary respiratory neurons of the cat.

Respiratory neurons were recorded intracellularly within the lateral region of the lower brain stem of vagotomized and artificially ventilated cats. Bulbospinal, vagal, and antidromically nonresponsive types of neurons were distinguished by means of vagal and intraspinal stimulation. Almost all types of neurons discharged a burst of action potentials during one of the two phases of the central respiratory cycle, as indicated by phrenic nerve activity. The discharge pattern of the different types of neurons were described. The origin of the spntaneous changes of the membrane potential was investigated by measurements of the reversal potentials and membrane conductance changes. The results reveal that both inspiratory and expiratory types of neurons receive an excitatory input during their discharge period, and a reciprocal inhibitory input during their silent period. In addition, one type of neuron was described which receives inhibitory inputs during both inspiration and expiration. Recurrent inhibition, as indicated by hyperpolarizing postsynaptic potentials and membrane conductance changes following the antidromic action potential seems to exist only within the network of the vagal neurons. Suggestions are made about the functional organization of the neuronal network of the medullary respiratory system and the mechanism generating its rhythmic activity.     

Inputs to intercostal motoneurons from ventrolateral medullary respiratory neurons in the cat

The investigation examined the synaptic input from medullary respiratory neurons in the nucleus retroambigualis (NRA) to external (EIM) and internal (IIM) intercostal motoneurons. Antidromic mapping revealed that 112/117 (96%) tested NRA units had axons descending into thoracic spinal cord with extensive arborizations at many thoracic segments, mainly contralaterally. The conduction velocities ranged from 10 to 105 m X s-1. The descending projections did not appear to be somatotopically arranged. Cross-correlation of the spike trains of NRA inspiratory units with the discharge of external intercostal nerves (performed usually with 4 contralateral nerves) showed significant narrow peaks only in 5 out of 40 averages. Of the 25 trigger units tested for the thoracic projection in this series of experiments, 24 were antidromically activated. Intracellular recordings were made from 52 IIMs [mean membrane potential 65.3 mV, central respiratory drive potentials (CRDPs) greater than 1 mV present in 23/52] and 53 EIM (mean membrane potential 54.3 mV, CRDPs in 31/53). During the depolarizing phase of the CRDPs, synaptic noise with frequent and apparently unitary EPSPs with amplitudes in excess of 1 mV was observed. Spike-triggered averages of synaptic noise were computed for 153 pairings between 137 NRA neurons and 105 contralateral intercostal motoneurons. Only four PSPs were revealed: two monosynaptic EPSPs between expiratory NRA units and IIMs and two probably disynaptic EPSPs between inspiratory NRA units and EIMs. When advancing the microelectrode down to the motoneuron pools, frequent recordings were made from interneurons with spontaneous respiratory discharge (inspiratory or expiratory) located dorsal and medial to the motor nuclei. The interneurons could be excited following stimulation of segmental afferents. It is concluded that monosynaptic connections between respiratory NRA neurons and intercostal motoneurons are rare (connectivity no more than approximately 4%). Segmental interneurons, interposed between the majority of descending respiratory axons and intercostal motoneurons, are likely to produce large unitary EPSPs and, thus, short-term synchronization in the discharge of intercostal motoneurons as observed by others.     

Synaptic mechanisms of inspiratory off-switching evoked by pontine pneumotaxic stimulation in cats

To elucidate synaptic mechanisms and the involvement of N-methyl-D-aspartate (NMDA) receptors in inspiratory off-switching (IOS) evoked by the stimulation of the nucleus parabrachialis medialis (NPBM), excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) were recorded from bulbar augmenting inspiratory (aug-I) and postinspiratory (PI) neurons in vagotomized cats. Stimulation of NPBM produced either transient inhibition or premature termination of inspiration (reversible or irreversible IOS), depending on the stimulus intensity. Each neuron displayed four-phasic postsynaptic responses during the reversible IOS, i.e. Phase 1 EPSPs, Phase 2 IPSPs, Phase 3 EPSPs and Phase 4 IPSPs in aug-I neurons, and Phase 1 plus 2 EPSPs, Phase 3 IPSPs and Phase 4 EPSPs in PI neurons. During the irreversible IOS, Phase 4 responses were replaced by sustained hyperpolarization in aug-I neurons and decrementing depolarization in PI neurons. Blockade of NMDA receptors by dizocilpine (0.3 mg kg(-1) i.v.) selectively increased Phase 4 potentials in both types of neurons and decreased the thresholds for evoking the irreversible IOS. The NPBM-induced responses had a pattern and time-course similar to those induced by vagal stimulation. The present results suggest that pneumotaxic and vagal inputs converge on the common IOS circuit, and the effectiveness of both inputs is modulated by NMDA receptors.     

Respiration-related control of abdominal motoneurons

The abdominal muscles form part of the expiratory pump in cooperation with the other expiratory muscles, primarily the internal intercostal and triangularis sterni muscles. The discharge of abdominal muscles is divided into four main patterns: augmenting, plateau, spindle and decrementing. The patterns tend to be species-specific and dependent on the state of the central nervous system. Recent studies suggest that the abdominal muscles are more active than classically thought, even under resting conditions. Expiratory bulbospinal neurons (EBSN) in the caudal ventral respiratory group are the final output pathway to abdominal motoneurons in the spinal cord. Electrophysiological and anatomical studies indicated the excitatory monosynaptic inputs from EBSN to the abdominal motoneurons, although inputs from the propriospinal neurons seemed to be necessary to produce useful motor outputs. Respiration-related sensory modulation of expiratory neurons by vagal afferents that monitor the rate of change of lung volume and the end-expiratory lung volume (EELV) play a crucial role in modulating the drive to the abdominal musculature. Studies using in vitro and in situ preparations of neonatal and juvenile rats show bi-phasic abdominal activity, characterized by bursting at the end of expiration, a silent period during the inspiratory period, and another burst that occurs abruptly after inspiratory termination. Since the abdominal muscles rarely show these post-inspiratory bursts in the adult rat, the organization of the expiratory output pathway must undergo significant development alterations.     

Intercostal and abdominal muscle afferent influence on caudal medullary expiratory neurons that drive abdominal muscles

Summary Our objective was to determine if caudal ventral respiratory group (VRG) expiratory (E) neurons that drive abdominal expiratory motoneurons in the lumbar cord respond to intercostal and lumbar nerve afferent stimulation. Results showed that 92% of medullary E-neurons that were antidromically activated from the upper lumbar cord reduced their activity in response to stimulation of external and internal intercostal and lumbar nerve afferents. We conclude that afferent information from intercostal and abdominal muscle tendon organs has an inhibitory effect on caudal VRG E-neurons that drive abdominal expiratory motoneurons.This study was supported by National Heart, Lung, and Blood Institute grant RO1-HL-17715     

Bötzinger-complex, bulbospinal expiratory neurones monosynaptically inhibit ventral-group respiratory neurones in the decerebrate rat

Extracellularly recorded action potentials from 49 Bötzinger-complex, bulbospinal expiratory neurones were used as triggers to compute 162 spike-triggered averages (STAs) of intracellular potentials recorded from 167 respiratory neurones in the ventral respiratory group (VRG) near the obex in 15 vagotomized, paralysed, ventilated and decerebrated rats. All of the Bötzinger-complex expiratory neurones were antidromically activated from the ipsilateral border between the C2/C3 segments of the spinal cord and discharged only during the late part of expiration with an augmenting pattern. We found evidence for monosynaptic inhibitory post-synaptic potentials (IPSPs) in 74 (～44%) of the STAs computed using 34 (～69%) of the trigger neurones. For vagal motoneurones, IPSPs were found in 24 of the 53 STAs of expiratory motoneurones, but in none of the 12 STAs of inspiratory motoneurones. For inspiratory neurones, IPSPs were found in 23 of the 33 STAs of bulbospinal neurones and in 6 of the 26 STAs of not antidromically activated (NAA) neurones. For expiratory neurones, IPSPs were found in one of the two STAs of bulbospinal neurones and in 20 of the 36 STAs of NAA neurones. We conclude that Bötzinger-complex, bulbospinal expiratory neurones monosynaptically inhibit bulbospinal inspiratory neurones, expiratory vagal motoneurones and other unidentified inspiratory and expiratory neurones in the VRG of rats during the late part of expiration.     

Extensive monosynaptic inhibition of ventral respiratory group neurons by augmenting neurons in the Bötzinger complex in the cat

Summary Axonal projections and synaptic connectivity of expiratory B?tzinger neurons with an augmenting firing pattern (Bot-Aug neurons) to neurons in the ipsilateral ventral respiratory group (VRG) were studied in anaesthetized cats. Antidromic mapping revealed extensive axonal arborizations of Bot-Aug neurons (24 of 45) to the rostral or caudal VRG, with some having arbors in both regions. Of 234 pairs of neurons studied with intracellular recording and spike-triggered averaging, monosynaptic inhibitory postsynaptic potentials (IPSPs) were evoked in 49/221 VRG neurons by 38/98 Bot-Aug neurons. The highest incidence of monosynaptic inhibition was found in inspiratory bulbospinal neurons (10 of 23 tested). Evidence was also found for monosynaptic inhibition, by a separate group of Bot-Aug neurons, of expiratory bulbospinal neurons (12/58), while excitatory postsynaptic potentials (EPSPs) were identified in another two of these neurons. In addition, monosynaptic IPSPs were recorded from 13 of 53 identified laryngeal motoneurons, and from 14 of 100 respiratory propriobulbar neurons. Presumptive disynaptic IPSPs were recorded from 11 of the 221 VRG neurons. We conclude that Bot-Aug neurons exert widespread inhibition on all major neuron categories in the ipsilateral VRG, and should be regarded as an important element in shaping the spatiotemporal output pattern of both respiratory motoneurons and premotor neurons.     

Decrementing expiratory neurons of the Bötzinger complex

Summary In Nembutal-anesthetized, immobilized and artificially ventilated cats, decrementing expiratory (E-DEC) neurons which were excited by lung inflation were isolated in the vicinity of the Bötzinger complex. Then intracellular recordings were made from the respiratory neurons in the contralateral ventral respiratory group (VRG). The intracellular membrane potentials were averaged using extracellular spikes of the E-DEC neurons as triggers (spike-triggered averaging method). Hyperpolarizing potentials locked to the triggering spikes were obtained and they were shown to be unitary IPSPs since their polarity was reversed when averaged during passage of hyperpolarizing current. The latencies of antidromic activation of the E-DEC-neurons from the area of intracellular recordings were shorter by about 0.2 ms than those of unitary IPSPs. This showed that the connections were monosynaptic. A total of 47 pairs were analyzed and unitary IPSPs were found in 12 pairs. The E-DEC neurons inhibited both inspiratory and expiratory neurons, including bulbospinal inspiratory neurons, propriobulbar inspiratory neurons, and vagal motoneurons with expiratory activity. These inhibitory E-DEC neurons, receiving excitatory inputs from the stretch receptors of the lungs, presumably intervene in reflex loops such as the Hering-Breuer reflex and may make some contribution to normal breathing.Supported by grants-in-aid for science research nos. 60304044, 62570068 from the Japan Ministry of Education, Science and Culture     

The role of dorsal respiratory group neurons studied with cross-correlation in the decerebrate rat

We examined the role of dorsal respiratory group (DRG) inspiratory neurons as transmitters of respiratory drive to phrenic and intercostal motoneurons and as relays of afferent information to ventral respiratory group (VRG) bulbospinal, inspiratory neurons. Attempts to antidromically activate 76 DRG neurons from the spinal cord at the C7 segment resulted in only 4 (5.3%) successes (3 contralateral, 1 ipsilateral). Cross-correlating DRG neuron discharge with that of the ipsilateral (56) and contralateral (20) phrenic nerve detected common activation peaks in 2 and 3 cases respectively, with no evidence for monosynaptic connections. Cross-correlating DRG neuron discharge with that of bulbospinal, inspiratory VRG neurons found some evidence for interaction. Peaks in 7 of 73 (10%) cross-correlation histograms were attributed to a monosynaptic excitation of DRG neurons by VRG neurons, although a common activation cannot be ruled out; troughs, some with an accompanying peak, in 9 (12.3%) histograms were interpreted as a combined excitation of the DRG neuron and delayed inhibition of the VRG neuron. In addition, 2 cross-correlation histograms showed peaks with latencies and half-amplitude widths consistent with a disynaptic excitation of a DRG neuron by a bulbospinal inspiratory VRG neuron. Cross-correlating the discharge of 57 pairs of DRG inspiratory neurons (6 contralateral) detected common activation peaks in 7 (12.3%) cases (none contralateral) and one case interpreted as evidence for a disynaptic excitation. These findings suggest that the role of the DRG inspiratory neurons in rats differs from that in cats, primarily because they do not act to transmit respiratory rhythmic drive directly to phrenic and intercostal motoneurons. The results offer some support for an excitation of DRG neurons by VRG inspiratory neurons, but no support for a role of DRG inspiratory neurons as mediators of afferent information transfer to VRG bulbospinal inspiratory neurons.     

Monosynaptic excitation of medullary inspiratory neurons by bulbospinal inspiratory neurons of the ventral respiratory group in the cat

Summary In Nembutal-anesthetized, immobilized, and artificially ventilated cats, we studied the connectivity of medullary collaterals of bulbospinal inspiratory (BS-I) neurons in the ventral respiratory group (VRG). BS-I neurons which projected to the contralateral spinal cord were isolated extracellularly and intracellular recordings were made from the respiratory neurons in the contralateral VRG. The intracellular membrane potentials were averaged using extracellular spikes of the BS-I neurons as triggers (spike-triggered averaging method). Fast-rising and short-lasting depolarizing potentials locked to the triggering spikes were obtained and shown to be unitary EPSPs induced monosynaptically by the medullary collaterals of BS-I neurons. A total of 137 pairs were analyzed and unitary EPSPs were found in 11 pairs. Four BS-I neurons and 7 inspiratory vagal motoneurons received EPSPs from the medullary collaterals of BS-I neurons. These findings suggest that 1) BS-I neurons in the VRG drive medullary motoneurons of accessory respiratory muscles and phrenic or intercostal motoneurons simultaneously, 2) BS-I neurons on both sides synchronize via the excitatory connections, and 3) the augmenting firing pattern of BS-I neurons might partly be produced by this reexcitatory connection within the population of BS-I neurons.     

Respiratory interneurons of the lower cervical (C4-C5) cord: membrane potential changes during fictive coughing,vomiting, and swallowing in the decerebrate cat

The possible roles of interneurons in the C4-C5 cervical spinal cord in conveying central drives to phrenic motoneurons during different behaviour patterns were investigated using intracellular recordings in decerebrate, paralysed, artificially ventilated cats. Eleven cells were tentatively classified as respiratory interneurons since they: (i) could not be antidromically activated from the ipsilateral whole intrathoracic phrenic nerve, and (ii) exhibited large membrane potential changes during eupnea (7.3 mV±3.6, range 2–13.5 mV) or non-respiratory behaviour patterns. Six neurons depolarized in phase with phrenic discharge; four others depolarized during the expiratory phase; one neuron exhibited depolarization during the end of both expiration and inspiration. A variety of responses was observed during fictive coughing, vomiting, and swallowing. The results are consistent with C4-C5 expiratory interneurons conveying inhibition to phrenic motoneurons during different behaviour patterns. The responses of inspiratory and multiphasic neurons suggest that the roles of these interneurons are mode complex than simply relaying central excitatory or inhibitory drive to phrenic motoneurons.     

Selective actions of anesthetic agents on membrane potential trajectory in bulbar respiratory neurons of cats

The effects of two anesthetic agents, halothane and thiopental, on the membrane potential trajectory of respiratory-related neurons in the ventral respiratory group were investigated in decerebrate cats, of which the carotid sinus and vagal afferents were denervated. Infusion of halothane (2% for 90 s) depolarized the membrane in nearly half of the inspiratory (12/21), post-inspiratory (10/26) and expiratory (4/6) neurons and caused hyperpolarization in the rest of the population. Thiopental (2.5 mg/kg i.v.) produced depolarization in 11 inspiratory and 10 post-inspiratory neurons and hyperpolarization in 1 expiratory, 4 inspiratory and 7 postinspiratory neurons. In both hyperpolarized and depolarized neurons, reduction of the respiratory membrane potential fluctuations and an increase of input resistance were commonly observed. Both drugs depressed spontaneous firing in most of the neurons studied. An increase of firing was observed in 9 out of 47 depolarized cells. These two contrasting effects on the membrane potential trajectory occurred similarly in the known groups of respiratory neurons, but the response of a given cell was consistent for the two anesthetic agents. The present results demonstrate that the anesthetic drugs exert various influences on the ventral respiratory group neuron population in maintaining the membrane potential trajectory and discharge activity. This may reflect a functional heterogeneity in the bulbar respiratory network of neurons.     

Reflex prolongation of stage I of expiration

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

Analysis of activity of motor units in the biceps brachii muscle after intercostal-musculocutaneous nerve transfer

We examined respiratory activity of motor units (MUs) in the internal intercostal nerves (IICNs)-transferred biceps brachii muscle (IC-biceps) in cats. MUs of IC-biceps showed respiratory discharges in inspiratory and expiratory phases, and these were enhanced by CO2 inhalation. Narrowing the airway also enhanced inspiratory and expiratory MUs activity. A mechanical load to the thorax immediately enhanced inspiratory MUs activity and weakened expiratory MUs activity. We analyzed the cross-correlation of MUs activity in interchondral muscle and IC-biceps to characterize the respiratory spinal descending inputs to motoneurons. We confirmed the short-term synchronization from interchondral muscles indicating divergence of a single respiratory presynaptic axon to thoracic motoneurons, but could not find synchronization from IC-biceps. The motor axonal conduction velocity (axonal CV) of IC-biceps MUs was lower than that of interchondral muscles. There was no correlation between the respiratory recruitment order of IC-biceps MUs and their axonal CV. These results indicate that IC-biceps shows the respiratory activities and afferent inputs from intercostal muscle spindles in the neighboring segments remain influential on activity of IC-biceps. In addition, the short-term synchronization from IC-biceps could not be found, suggesting that the intercostal nerve transfer alters the respiratory spinal descending inputs to thoracic motoneurons.     

Medullary respiratory neural activity during hypoxia in NREM and REM sleep in the cat

Intact unanesthetized cats hyperventilate in response to hypocapnic hypoxia in both wakefulness and sleep. This hyperventilation is caused by increases in diaphragmatic activity during inspiration and expiration. In this study, we recorded 120 medullary respiratory neurons during sleep in hypoxia. Our goal was to understand how these neurons change their activity to increase breathing efforts and frequency in response to hypoxia. We found that the response of medullary respiratory neurons to hypoxia was variable. While the activity of a small majority of inspiratory (58%) and expiratory (56%) neurons was increased in response to hypoxia, the activity of a small majority of preinspiratory (57%) neurons was decreased. Cells that were more active in hypoxia had discharge rates that averaged 183% (inspiratory decrementing), 154% (inspiratory augmenting), 155% (inspiratory), 230% (expiratory decrementing), 191% (expiratory augmenting), and 136% (expiratory) of the rates in normoxia. The response to hypoxia was similar in non-rapid-eye-movement (NREM) and REM sleep. Additionally, changes in the profile of activity were observed in all cell types examined. These changes included advanced, prolonged, and abbreviated patterns of activity in response to hypoxia; for example, some inspiratory neurons prolonged their discharge into expiration during the postinspiratory period in hypoxia but not in normoxia. Although changes in activity of the inspiratory neurons could account for the increased breathing efforts and activity of the diaphragm observed during hypoxia, the mechanisms responsible for the change in respiratory rate were not revealed by our data.     

Activity of respiratory laryngeal motoneurons during fictive coughing and swallowing

Membrane potential changes and discharges from 28 laryngeal motoneurons were recorded intracellularly in the caudal nucleus ambiguus of decerebrate, paralyzed and ventilated cats. Electrical activities were recorded from 17 expiratory laryngeal motoneurons (ELMs) with maximal depolarizing membrane potential in early expiration, and from 11 inspiratory laryngeal motoneurons (ILMs) with maximal depolarizing membrane potential in inspiration. Activities during breathing were compared with those observed during fictive coughing and swallowing evoked by electrical stimulation of the superior laryngeal nerves. These non-respiratory behaviors were evidenced in paralyzed animals by characteristic discharge patterns of the phrenic, abdominal nerves and pharyngeal branch of the vagus nerve. We recorded the activity of 11 ELMs and 5 ILMs during coughing in which ELMs, but not ILMs, exhibited increased membrane depolarization and discharge frequencies. Membrane depolarization and discharge frequencies of all ELMs were also significantly increased during swallowing. In addition, membrane depolarization of most ELMs (15/17) was preceded by a short-lasting hyperpolarization due to chloride-dependent inhibitory mechanisms occurring at the onset of swallowing. Out of 10 ILMs tested during swallowing, 7 exhibited membrane depolarization, preceded in 5 cases by a short-lasting hyperpolarization. Discharge frequencies of ILMs were significantly reduced during swallowing. The same pattern of phasic activities of ILMs and ELMs was observed during coughing and breathing, suggesting the involvement of similar excitatory pathways in both behaviors. These results imply that the duration of activation and the discharge frequency of neurons of the central generator for breathing that drive laryngeal motoneurons are enhanced during coughing. During swallowing, in addition to central excitatory mechanisms, laryngeal motoneurons are subjected to an initial inhibition of unknown origin. This inhibition probably contributes to the temporal organization of the swallowing motor sequence. Received: 3 December 1998 / Accepted: 26 June 1999