Inspiratory Discharge Research Articles

Pneumotaxic mechanisms in the non-human primate: Effect of the [formula omitted] (NMDA) antagonist ketamine

We tested the possible involvement of N- methyl- d-aspartate (NMDA) receptors in the central inspiratory-termination mechanism in non-human primates. Inspiratory bursts were recorded from the phrenic nerve in Macaca fascicularis monkeys paralyzed and ventilated by means of a servoventilator driven by the inspiratory discharge of the phrenic nerve. The central inspiratory termination mechanism was tested by withholding lung inflation. This transiently suppressed the vagal feedback from the lungs which produces inspiratory off-switching independent from the central mechanism. Under anaesthesia with ketamine, a potent NMDA antagonist, non inflation increased inspiratory time to 4 s (1 s with lungs inflated) whereas no such effect was observed during halothane anaesthesia. We conclude that the termination of inspiration in primates is controlled via central mechanisms in which NMDA receptors are involved.

Rapidly adapting receptors monitor lung compliance in spontaneously breathing dogs

We examined the ability of rapidly adapting receptors (RARs) to monitor changes in dynamic lung compliance (Cdyn) in anesthetized spontaneously breathing dogs by recording RAR impulses from the vagus nerves. We decreased Cdyn in steps through the physiological range by briefly restricting lung expansion with an inflatable cuff around the chest and recording the response after deflating the cuff; we restored Cdyn to control by hyperinflating the lungs. Of 45 RARs, 34 were stimulated by a 40 +/- 2% reduction in Cdyn, their inspiratory discharge increasing on average more than threefold. Two-thirds of responsive RARs were stimulated by less than or equal to 20% reductions in Cdyn; in most, firing increased proportionately with lung stiffness (1/Cdyn) as Cdyn was decreased further. Stimulation by reduced Cdyn was not simply a function of the concomitant increase in transpulmonary pressure, because similar increases in pressure produced by increasing tidal volume produced smaller increases in firing. RAR stimulation was unaffected by atropine and, hence, was not dependent on neurally mediated changes in bronchomotor tone. Our results indicate that during spontaneous breathing RARs provide a signal inversely proportional to Cdyn.

Respiratory activity in retrotrapezoid nucleus in cat

An anatomic projection from the retrotrapezoid nucleus to the ventral respiratory group in cat was previously reported by our laboratory (J. C. Smith, D. E. Morrison, H. H. Ellenberger, M. R. Otto, and J. L. Feldman. J. Comp. Neurol. 281: 69-96, 1989). We now report on the properties of neurons in the retrotrapezoid nucleus, investigated with extracellular recording techniques in 10 chloralose-urethane anesthetized, paralyzed, mechanically ventilated cats. A ventral exposure of the medulla facilitated recording from neurons in the retrotrapezoid nucleus, located ventral to the facial nucleus near the medullary surface. Respiratory-modulated, as well as irregularly discharging, spontaneous unit activity was recorded within the retrotrapezoid nucleus. Twelve respiratory-modulated units in the retrotrapezoid nucleus exhibited inspiratory (8 units), expiratory (3 units), or multimodal (1 unit) discharge patterns. Chemical activation of an inspiratory unit in the retrotrapezoid nucleus by pressure ejection of DL-homocysteic acid (less than 0.5 nl of 10 mM solution) demonstrated that the respiratory-modulated activity originated from the cell soma and not fibers of passage coursing through the retrotrapezoid nucleus region. Electrical microstimulation (20-40 microA, approximately 70-microseconds duration, biphasic pulse) within the ipsilateral ventral respiratory group elicited antidromic activation of 7 units in the retrotrapezoid nucleus, three of which were not spontaneously active. Electrical stimulation (5-80 microA, 70-microseconds pulse width, 100 Hz, 400- to 500-ms trains) at sites within retrotrapezoid nucleus affected the respiratory motor output when delivered during late expiration, eliciting premature onset of inspiration. These results suggest that retrotrapezoid nucleus projections to the ventral respiratory group (and dorsal respiratory group) may influence respiratory timing and pattern, perhaps by conveying signals originating in the rostral ventrolateral medulla that result from ventral surface perturbations.

Effects of histamine on slowly adapting pulmonary stretch receptor activities in vagotomized rabbits.

Thirty-two SAR fibers located below the carina were used in 32 anesthetized, bilaterally vagotomized, and artificially ventilated rabbits. After intravenous administration of histamine (20, 40, and 80 micrograms/kg, n = 13) or ACh (10, 20, and 40 micrograms/kg, n = 13), SARs became active during expiration but decreased their inspiratory activity. The effects of both drugs were dose-dependent. The injection of histamine or ACh at all doses examined had no effect on tracheal pressure (PT). Atropine (3 mg/kg) and isoprenaline (100 micrograms/kg) blocked the responses of SAR activity to low doses of histamine (20 and 40 micrograms/kg) and to all doses of ACh. The response of SARs to 80 micrograms/kg of histamine was not altered by atropine (n = 10) nor by isoprenaline (n = 10). These results suggest that low-dose effects of histamine on SARs occur as the result of ACh release whereas with high doses the effect of histamine on the receptors is mainly independent of ACh released from the nerve endings. In another series of experiments (n = 6) where animals were treated with isoprenaline (100 micrograms/kg) and, subsequently, physostigmine (200 micrograms/kg), histamine (20 and 40 micrograms/kg) or ACh (10 and 20 micrograms/kg) increased the inspiratory discharge in SARs and the level of PT. From these results, it is assumed that the changes of SAR activity following histamine injection in vagotomized animals reflect a local bronchomotor effect which takes place in a peripheral bronchial tree that does not affect the level of PT. Histamine seems to release ACh and to elicit bronchoconstriction that can be manifested by physostigmine treatment.

Tonic activity in inspiratory muscles and phrenic motoneurons by stimulation of vagal afferents.

In anesthetized rabbits, direct and integrated phrenic neurogram (Ephr) and electromyograms from the diaphragm (Edi) and intercostal (Eic) (2nd space) and transversus abdominis muscles (Etr) were simultaneously recorded in two protocols. 1) In animals breathing spontaneously, we used infinite inspiratory (RI) or expiratory (RE) resistive load and intravenous injections of carbachol, histamine, or phenyl diguanide (PDG). All circumstances except RE evoked tonic activities in Ephr, Edi, and Eic but never in Etr. Intravenous atropine abolished carbachol-induced bronchoconstriction and associated tonic inspiratory activities, but this effect persisted with RI, histamine, and PDG. Selective procaine block of conduction in thin vagal fibers (with persistence of the Breuer-Hering inflation reflex) reduced or suppressed the tonic response, which was abolished in all cases after vagotomy. 2) In rabbits artificially ventilated with open chest, passive deflation of the lung or intravenous injections of histamine or PDG also produced tonic discharge in Ephr and often in Eic. The present results demonstrate that 1) stimulation of vagal afferents and mostly thin sensory fibers elicits tonic inspiratory discharges, 2) bronchoconstriction is not necessary for the induction of the response, and 3) reflexes from the chest wall do not mediate this response in rabbits.

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.

Synaptic rhythm of caudal medullary expiratory neurones during stimulation of the hypothalamic defence area of the cat.

1. Intracellular recordings were made from caudal medullary expiratory neurones in anaesthetized, paralysed, artificially ventilated and vagotomized cats before during and after the tachypnoeic response evoked by stimulation of the perifornical region of the hypothalamus. 2. The tachypnoeic response was evoked in seven of ten cats tested, and was represented in the phrenic nerve by a rapid two- to threefold increase in the frequency of the respiratory rhythm. The shortened duration of inspiratory discharge in the phrenic nerve was accompanied by an increase in its rate of development. If initially present, post-inspiratory phrenic discharge was intensified and extended throughout the shortened expiratory interval. 3. Intracellular recordings were obtained from twenty-one expiratory neurones during intermittent hypothalamic stimulation with short trains of pulses. Eighteen neurones showed a regular, short-latency sequence of synaptic events which consisted of an initial depolarizing potential (presumed EPSP) and a following hyperpolarizing potential (Cl--mediated IPSP) of long duration (50-150 ms when measured in expiration). The IPSP was accompanied by a phasic cessation of phrenic nerve discharge of comparable duration which was succeeded by intensified discharge. In three neurones (one experiment) the IPSP response was absent. 4. Sixteen neurones showing the EPSP-IPSP sequence were held for sufficiently long to record changes in the respiratory-related membrane potential pattern accompanying stimulation. The reduced expiratory time accompanying the response resulted in a shortened expiratory burst. In four neurones showing evidence of IPSPs in early expiration (post-inspiratory IPSPs), stimulation resulted in a phasic weakening of this inhibition which resulted in a more rapid approach to threshold and a steady rather than delayed increase in discharge. A low level of post-inspiratory IPSPs extended throughout most of the shortened expiration, resulting in an alternating rhythm of inspiratory and post-inspiratory inhibition. In the twelve neurones lacking such post-inspiratory IPSPs stimulation had no obvious effect on the shape of the expiratory trajectory. 5. In neurones which received an IPSP from hypothalamic stimulation, the overall response was associated with reduced amplitude and increased rate of decline of inspiratory inhibition of expiratory neurones. Three neurones showed high-frequency (70-80 Hz) oscillation of the membrane potential during inspiration (Mitchell & Herbert, 1974b). Hypothalamic stimulation resulted in a transient suppression of this oscillation. 6. We conclude that the short-latency inhibitory component of the response to hypothalamic stimulation is widely distributed, including expiratory neurones, some fraction of the inspiratory population and the neurones responsible for inspiratory and post-inspiratory inhibition.

Correlated and uncorrelated high-frequency oscillations in phrenic and recurrent laryngeal neurograms.

1. Power spectral analysis of phrenic and recurrent laryngeal (or efferent vagal) inspiratory discharge activity from anesthetized cats revealed a peak within the 60- to 110-Hz range in all spectra, plus a peak within the 40- to 60-Hz range in the laryngeal (and efferent vagal) spectra, and a peak less than 40 Hz in the phrenic spectra. 2. A 60- to 110-Hz peak was present in coherence spectra between the left and right phrenic neurograms, the left and right recurrent laryngeal (and efferent vagal) neurograms, and all combinations of phrenic-laryngeal (and phrenic-efferent vagal) pairs. It is concluded that the nearly-periodic oscillations represented by these peaks arise from a single source that projects functionally in parallel to many respiratory motor outputs. This source may be part of, or interact with, respiratory central pattern generation. 3. The 40- to 60-Hz oscillations in left and right recurrent laryngeal (and efferent vagal) neurograms were uncorrelated or occasionally were very weakly correlated. Thus it is unlikely that these oscillations arise from a common source such as a second respiratory central pattern generator. 4. The oscillations less than 40 Hz were weakly correlated between left and right phrenic neurograms. This correlation may be due substantially to spinal crossed-phrenic pathways. 5. It is proposed that both the 40- to 60-Hz oscillations in recurrent laryngeal neurograms and the oscillations below 40 Hz in phrenic neurograms originate in neural circuits associated with individual left or right recurrent laryngeal or phrenic motor outputs. 6. Our results do not support the interpretation that multiple peaks in phrenic and recurrent laryngeal power spectra are due to two respiratory central pattern generators whose outputs have parallel pathways to respiratory motoneurons.

Connectivity of slowly adapting pulmonary stretch receptors with dorsal medullary respiratory neurons.

1. Intracellular recordings were made from 50 dorsal respiratory group (DRG) neurons in the region of the ventrolateral nucleus of the solitary tract in anesthetized, paralyzed cats ventilated with a cycle-triggered pump whose inflation stroke was triggered by the onset of phrenic nerve inspiratory (I) discharge. Activity was recorded simultaneously in the ipsilateral nodose ganglion from sensory cell bodies of slowly adapting pulmonary stretch receptors (PSRs). 2. Respiratory cycle-related membrane potential changes of DRG neurons were recorded. Twenty-six neurons that did not exhibit spikes were classified as I alpha, I beta or pump (P)-cells by comparing their membrane potential trajectories during I in the presence of lung inflation with that observed during I, but with lung inflation withheld. The remaining 24 neurons were classified similarly, but the classification was based upon a comparison of their I-phase spike activity responses with and without lung inflation. I phase-related histograms of either membrane potential or spike activity were constructed to facilitate DRG neuronal classification. Additionally, steady lung inflation of varying magnitudes was applied during the expiratory phase. This prolonged expiration and produced different responses in the neurons. Generally, I beta and P-cells were depolarized, whereas I alpha cells were hyperpolarized. 3. Low-intensity electrical stimulation of the ipsilateral vagus nerve evoked excitatory postsynaptic potentials (EPSPs) in all three DRG neuronal types. P-cells and I beta cells exhibited EPSPs in response to the lowest intensity; generally this intensity was below threshold for the simultaneously recorded PSR. Overall, EPSPs in I alpha cells had the highest thresholds, but some EPSPs could be evoked at thresholds similar to those of the I beta cells. The distributions of the average onset latency of the evoked EPSP overlapped considerably. Thus vagal electrical stimulation cannot be used for unequivocal classification of DRG neurons into I alpha, I beta, and P-cell subpopulations. 4. Using intracellular spike-triggered averaging, single PSRs were shown to generate monosynaptic EPSPs in I beta neurons and P-cells but not I alpha cells. Divergence of single PSR afferents also was observed. Relationships between EPSP shape factors, amplitudes, and PSR afferent conduction velocity are similar to those previously observed for monosynaptic EPSPs in hindlimb motoneurons generated by spinal afferents.

Phrenic and external intercostal motoneuron activity during progressive asphyxia.

Phrenic and external intercostal motoneuron activities were compared during progressive asphyxia induced by the interruption of artificial ventilation in the pentobarbital-urethan-anesthetized, gallamine-paralysed rabbit. The relative augmentation of inspiratory activity of the T1-T4 external intercostal nerves was significantly greater than that of the phrenic nerve during asphyxic hyperpnea. This was associated with a greater recruitment of intercostal than of phrenic motoneurons, particularly late in the hyperpneic phase immediately before the period of asphyxic apnea. However, peak and average discharge frequencies developed by intercostal motoneurons (n = 20) were only approximately 60% of those of the phrenic motoneurons (n = 28). Gasping respiration terminated the apneic period and was associated with a further intense recruitment of intercostal though not of phrenic motoneurons, but discharge frequencies developed by the intercostal motoneurons remained approximately 60% of those of the phrenic motoneurons. The instantaneous frequency profiles generated by the motoneurons often exhibited progressive changes during the terminal stages of hyperpnea (reduction in inspiratory duration and duty cycle and increases in inspiratory slope and discharge frequencies) such that much of the character of gasping respiration became evident before the apnea. Such smooth transitional sequences do not obviate the existence of an "independent gasping center" but do require that such a proposed center at least possess the capacity for interaction with those sites responsible for the generation of eupneic and hyperpneic respiration.

Acute effect of cigarette smoke on laryngeal receptors.

Upper airway exposure to cigarette smoke elicits reflex changes in breathing pattern. To examine whether laryngeal afferents are affected by cigarette smoke, neural activity was recorded from the peripheral cut end of superior laryngeal nerve in anesthetized dogs. A box-balloon system, connected to the breathing circuit, allowed smoke to be inhaled spontaneously through the isolated upper airway while preserving its normal respiratory flow and pressure. Our results showed the following. Inhalation of cigarette smoke (25-50% concentration, 300-400 ml) caused a marked increase in activity of laryngeal irritant receptors which were either silent or randomly discharging during control breathing [their activity increased from a control value of 1.67 +/- 0.50 (mean +/- SE; n = 21) to a peak of 5.03 +/- 0.85 impulses/s in 11-15 s]. The activity of laryngeal cold receptors was reduced to 77.3 and 63.8% of control (n = 9) during the two breaths of smoke inhalation, respectively. After returning toward the base-line activity, a more pronounced inhibition (26.3% of control) occurred at three to nine breaths after the smoke inhalation. A small but significant decrease (88.5% of control) in the inspiratory discharge of laryngeal mechanoreceptors was observed during the first test breath. These effects were independent of the CO2 content of the smoke. Furthermore, there was no difference between the responses of these laryngeal afferents to high- and low-nicotine cigarette smoke.

O-21 - Effect of pentobarbital on the coherent relationship between high frequency oscillations in inspiratory discharges of the phrenic and cranial nerves

O-21 - Effect of pentobarbital on the coherent relationship between high frequency oscillations in inspiratory discharges of the phrenic and cranial nerves

Serotoninergic and non‐serotoninergic responses of phrenic motoneurones to raphe stimulation in the cat.

Experiments were conducted on anaesthetized, paralysed and artificially ventilated cats in order to determine if the altered discharge pattern of phrenic motoneurones recorded during stimulation of medullary raphe nuclei (raphe magnus (r. magnus), raphe obscurus (r. obscurus), raphe pallidus (r. pallidus] are related to release of serotonin (5-hydroxytryptamine, 5-HT) at synapses on respiratory neurones. Effects of 5-HT released by the neurotoxin p-chloroamphetamine (PCA) on spontaneous activity of phrenic motoneurones were also examined. In addition, responses of phrenic motoneurones to 5-HT applied by micro-electrophoresis were recorded. Stimulation (100 Hz) of r. magnus or r. obscurus depressed the spontaneous inspiratory discharges of phrenic motoneurones. Administration of the 5-HT receptor antagonists cinanserin, methysergide or methergoline reduced, but did not abolish, the inhibition. Inhibition of the neuronal reuptake of 5-HT with fluoxetine enhanced the inhibition and reduced the peak inspiratory action potential frequency of spontaneous discharges. Stimulation (100 Hz) of r. pallidus produced increased firing of phrenic motoneurones. Firing of phrenic motoneurones was evoked even during the normally quiescent expiratory phase of spontaneous respiratory activity. Antagonists at 5-HT receptors reduced the degree of tonic firing, resulting in partial restoration of expiratory pauses during r. pallidus stimulation. Inhibition of 5-HT reuptake, on the other hand, resulted in increased tonic firing. Release of 5-HT by PCA produced a rapid and severe reduction of phrenic nerve activity. Activity was restored by 5-HT receptor antagonists. In reserpine-treated cats, effects of stimulating medullary raphe nuclei were still pronounced, however 5-HT receptor antagonists had no effect on the responses. These results, along with the observation that 5-HT receptor antagonists are only partially effective in non-reserpinized cats, indicate that non-serotoninergic influences contribute as well to the responses evoked by raphe stimulation. Micro-electrophoretic application of 5-HT by large ejecting currents (100-200 nA) had weak stimulatory effects on twenty of forty-five phrenic motoneurones, which exhibited small increases in peak inspiratory discharge frequency during 5-HT application. Ejecting currents less than 100 nA were without effect. It is concluded that 5-HT analogues and agents which release endogenous 5-HT after parenteral administration do not act directly at synapses on the soma membranes of phrenic motoneurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Responses of phrenic motoneurones of the cat to stimulation of medullary raphe nuclei.

Responses of phrenic motoneurones to stimulation of the three medullary raphe nuclei (raphe magnus (r. magnus), raphe obscurus (r. obscurus) and raphe pallidus (r. pallidus] were recorded in anaesthetized and decerebrated cats. Stimulation of r. magnus or r. obscurus depressed phrenic motoneurones. Stimulation at 100 Hz reduced action potential frequency within each inspiratory burst, without appreciable changes in inspiratory duration, or number of inspiratory bursts per unit time. The depression was proportional to the stimulus intensity (40-160 microA) and frequency (12-100 Hz) and lasted throughout the period of stimulation. Intracellular recording revealed concomitant depression of central respiratory drive potentials (c.r.d.p.s) and increased membrane input resistance during r. obscurus or r. magnus stimulation. In motoneurones which discharged action potentials during expiratory as well as inspiratory phases following intracellular chloride injection, stimulation of r. magnus or r. obscurus depressed cell firing during both phases. Both c.r.d.p.s and reversed inhibitory post-synaptic potentials (i.p.s.p.s) were depressed. These findings indicate that the depression is not related to post-synaptic inhibition of phrenic motoneurones. Stimulation (100 Hz) of r. pallidus produced discharges of action potentials in phrenic motoneurones. Stimulation lengthened the duration of each inspiratory discharge in proportion to stimulus intensity. Continuous firing occurred throughout the period of stimulation with maximal intensities. Intracellular recordings revealed sustained depolarization and reduction in membrane input resistance during the discharge. Responses were recorded extracellularly from medullary inspiratory neurones of the dorsal respiratory group (d.r.g.) and ventral respiratory group (v.r.g.) and from vagal axons which fired in phase with phrenic nerve activity. Responses to raphe stimulation were similar to those recorded from phrenic motoneurones. Evidence is presented that the responses are not related to stimulation of decussating bulbo-spinal axons from d.r.g. or v.r.g. neurones. It is suggested that medullary respiratory neurones receive inhibitory and excitatory synaptic inputs from medullary raphe neurones. Hypercapnia (5% CO2 in O2) or hypoxia (15% O2 in N2) reduced markedly the inhibition produced during stimulation of r. obscurus or r. magnus, and restored expiratory-linked silent periods during stimulation of r. pallidus. Activation of Hering-Breuer or baroreceptor reflexes did not alter responses to r. pallidus stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Changes in intrapulmonary chemoreceptor discharge in response to the adjustment of respiratory pattern during hyperventilation in domestic fowl.

It has been suggested that avian vagal intrapulmonary CO2-sensitive receptors (i.p.c.) may be capable of monitoring the rate and extent of CO2 wash-out from the lung during spontaneous breathing. The purpose of this study was to record i.p.c. discharge activity in spontaneously breathing domestic fowl when minute volume (VI) was elevated from resting levels. This was accomplished by administration of almitrine (2 mg X kg-1 I.V.), a respiratory stimulant drug that has been shown to have a specific long-lasting stimulatory action on carotid body chemoreceptors. Unanaesthetized decerebrate fowl were tracheotomized and single-unit activity was recorded from sixteen vagal i.p.c. When ventilation was elevated 2.2-fold by almitrine (initially by increases in tidal volume (VT)) i.p.c. discharge was increased in both inspiration and expiration, and the delay period before the onset of i.p.c. discharge in inspiration was markedly shortened. Within 5-10 min after the administration of almitrine, the breathing pattern changed to one of rapid, shallow breathing, although the 2.2-fold elevation of the rate of gas flow through the parabronchi (V) and mean inspiratory flow rate (VT/TI) were maintained. The i.p.c. continued to fire phasically, with peaks of discharge in both inspiration and expiration, though there were fewer spikes per breath and mean inspiratory peak discharge rate returned to control (eupnoeic) levels. It is concluded that i.p.c. discharge is increased when VI is elevated in the spontaneously breathing fowl and that the pattern of discharge is dependent on the pattern of breathing. I.p.c. show high dynamic sensitivity to changes in the PCO2 of their microenvironment and it is possible to explain the changes in discharge pattern observed in terms of the PCO2 changes in the lungs and air sacs. These results support proposals that the pattern of breathing is to some extent dependent upon the intensity and timing of i.p.c. activity.

Split medulla preparation in the cat: arterial chemoreceptor reflex and respiratory modulation of the renal sympathetic nerve activity

The study was undertaken in order to assess the changes in sympathetic output in a split medulla preparation of the cat which, as shown earlier, has impaired respiratory rhythm generation. The effects of medullary midsagittal sections on renal sympathetic nerve firing were investigated in chloralose anesthetized, paralyzed and artificially ventilated cats. Recordings of phrenic and recurrent laryngeal nerve activity served as indices of central respiratory rhythm generation. Sections, 5 mm deep from the dorsal medullary surface and extending 6 mm rostrally and 3 mm caudally to the obex, did not produce any significant changes in heart rate, blood pressure or tonic renal sympathetic nerve firing levels. They decreased or abolished, however, the respiratory rhythmicity in renal sympathetic nerve which paralleled the reduction of inspiratory discharges in phrenic and recurrent laryngeal nerves, and abolished the carotid body chemoreceptor-sympathetic reflex. The inspiratory activity remaining after the sections could still be enhanced by chemoreceptor stimulation. The inhibitory baroreceptor and pulmonary stretch receptor sympathetic reflexes, and the central excitatory effect of CO 2 on renal sympathetic nerve firing were not altered. The effects of electrical stimulation within the midsagittal plane of the medulla have shown that descending pathways from the medullary inspiratory neurons (or their medullary collaterals) do not participate in the facilitation of spinal preganglionic neurons during inspiration and in relaying the pulmonary stretch receptor inhibitory sympathetic reflex. A region located close to the obex was identified from which excitatory responses in renal sympathetic nerves, compatible with the response obtained by carotid sinus nerve stimulation, could be evoked. It is concluded that a lesion in the midline of the lower medulla at the level of the obex selectively destroys cells or pathways which relay the carotid body chemoreceptor-sympathetic reflex.

Hypoglossal motoneuron responses to pulmonary and superior laryngeal afferent inputs

In decerebrate, paralyzed cats ventilated with a cycle-triggered pump, the inspiratory discharges of the hypoglossal (whole nerve or single fibers), phrenic, and recurrent laryngeal nerves were compared, and the effects of pulmonary and superior laryngeal inputs were observed. During lung inflations phase with neural inspiration, hypoglossal and recurrent laryngeal activities differed from phrenic with respect to (a) burst onset times: both preceded the phrenic; (b) overall pattern: phrenic, augmenting; hypoglossal, decrementing; recurrent laryngeal, plateau-like. When inflation was withheld, the phrenic pattern was not markedly changed, but both hypoglossal and recurrent laryngeal became augmenting; the marked increas of hypoglossal activity (both whole nerve and single fiber) indicated strong inhibition by lung afferents. Superior laryngeal electrical stimulation evoked excitation of the contralateral phrenic (latency 4.1 msec) and the ipsilateral whole hypoglossal (latency 5.3 msec), followed by bilateral inhibitions (durations 20–30 msec); most hypoglossal fibers showed only inhibition. We conclude that, although both hypoglossal and phrenic outputs are driven by the inspiratory pattern generator(s), their premotor systems differ with respect to influences from central and peripheral inputs.

Restoration of function in external intercostal motoneurones of the cat following partial central deafferentation.

The activity of external intercostal motoneurones in the cat was studied under anaesthesia and paralysis before and after partial central deafferentation caused by single or double ipsilateral hemisections of the thoracic spinal cord. The normal efferent inspiratory discharges recorded from external intercostal nerve filaments caudal to the upper lesion were greatly reduced acutely, but activity of approximately normal intensity and phase at eupneoic levels of CO2 was restored within a few days and remained at similar levels for up to two years. The patterns of the restored activity were abnormal, with more discharges of alpha-motoneutrones during expiration than normal and a stronger modulation of the discharges by the respiratory pump than normal. A common abnormal component of the restored activity was a tonic discharge in hypocapnic apnoea, often modulated by the respiratory pump. This activity was never seen in normal animals or in those with acute lesions under similar conditions of anaesthesia. Synchronization of the discharges of alpha-motoneurones caudal to the upper lesion was studied by constructing cross-correlation histograms between paired groups of motoneurones, each group being represented by the discharges in one filament. Synchronization was stronger than normal, usually extending over a time course of +/- 20 to +/- 50 ms (broad-peak synchronization). This synchronization was particularly strong for the discharges in hypocapnic apnoea. We conclude that the restored activity was derived in large part from abnormal tonic (non-respiratory-phased) inputs, partly proprioceptive in origin, probably involving spinal cord interneurones with abnormally synchronized discharges. This conclusion is supported by intracellular measurements including respiratory drive potentials, synaptic noise and average common excitation potentials.

Types and locations of respiratory-related neurons in lateral tegmental field of cat medulla oblongata

Extracellular microelectrode recordings were made from a total of 868 neurons in the medullas of cats in regions known to contain high densities of respiratory-related neurons (solitary tract complex, nucleus ambiguus/retroambigualis, lateral tegmental field). Both the discharge patterns and the locations of units were noted and correlated with a recently described substructure of the tegmental field of the cat medulla in which neuronal cell bodies are found associated with sheets of blood vessels supplying the brainstem 28,29. The majority of cells were phasically firing (59%) with activity confined to either the inspiratory or the expiratory phase, 21% were tonically firing cells with no discernible respiratory modulation and 20% were silent neurons, responsive to electrical stimulation of the vagus nerves or the dorsolateral pons in the vicinity of nucleus parabrachialis, but not to various respiratory stimuli. Within the solitary tract complex inspiratory discharge patterns were predominant (94%), while in nucleus ambiguus/retroambigualis 26% of the neurons had expiratory patterns with the rest being inspiratory (68%) or tonic (6%). Within the lateral tegmental field, the percentages of inspiratory, expiratory and tonic patterns were 51,9 and 40%. Thus, inspiratory type patterns were found throughout the medulla, but expiratory patterns were most common in the ambiguus/retroambigualis nuclei. Found within all 3 major regions, but primarily within the lateral tegmental field of the rostral medulla were neurons that discharged with a brief burst at the inspiratory to expiratory phase transition. These cells had properties consistent with the off-switch mechanism: extreme late-inspiratory onset of discharge with the onset time being delayed by lung inflation, peak discharge at or slightly after the peak activity of the diaphragmatic EMG and a discharge rate which was insensitive to lung inflation. Within the lateral tegmental field, where longitudinal sheets of blood vessels running radially with respect to the IVth ventricle have been described 29, it was found that 85% of the tonically active units and 93% of the respiratory modulated cells were located less than 200 μm from the planes of these sheets. In addition, 87% of the neurons that could be antidromically or synaptically activated from the dorsolateral rostral pons were similarly located.

Lengthening of inspiration by intrapulmonary chemoreceptor discharge in ducks.

The influence of avian intrapulmonary chemoreceptors (IPC) on inspiratory duration (TI) was tested by experimentally reducing their level of discharge for a single inspiration. The seven major air sacs of decerebrate or anesthetized ducks were cannulated with wide-bore tubing and then connected to a single clamped outlet. In self-ventilating animals, opening the sac line for a single inspiration caused the inspiratory discharge of 17 IPC to disappear and that of a further 7 to fall substantially; no IPC showed a rise in discharge, nor did the 6 presumed respiratory stretch receptors from which recordings were made. The reduction of IPC discharge was accompanied by a fall in TI rather than the rise required if IPC were to resemble mammalian pulmonary stretch receptors in their action on TI. We propose that in eupnea inspiratory IPC discharge prolongs inspiration.