Influence of pulmonary inflations on discharge of pontile respiratory neurons

The purpose of this study was to characterize the influence of pulmonary inflations on the discharge patterns of rostral pontile respiratory neurons. Decerebrate and paralyzed cats were ventilated with a servo-respirator which produced patterns of pulmonary inflation, assessed by tracheal pressure, which paralleled alterations in integrated activity of the phrenic nerve. Neurons with respiratory-modulated neuronal activities were recorded in the pneumotaxic region of the nucleus parabrachialis medialis and Kolliker-Fuse nucleus, as well as in the trigeminal motor nucleus. Approximately equal numbers of neurons had phasic and tonic respiratory-modulated discharge patterns. The discharge patterns of most neurons were not qualitatively altered when pulmonary inflation was prevented. However, withholding inflation did cause the recruitment of some respiratory-modulated neuronal activities. Similar findings were obtained in normocapnia and hypercapnia. Results support the concept that the discharge of neurons in the pneumotaxic region may exert phasic, as well as tonic, influences on ventilatory activity.     

Discharge patterns of phrenic motoneurons during fictive coughing and vomiting in decerebrate cats.

In decerebrate, paralyzed, and ventilated cats, we recorded the activity of 100 spontaneously active phrenic motor axons during the increased phrenic discharges characteristic of fictive vomiting (FV) and coughing (FC). During control respiratory cycles, approximately one-half the neurons were recruited in the first decile of inspiration; recruitment continued throughout inspiration. During FV, the duration of phrenic discharge was halved; 20 of 26 motoneurons studied were recruited in the first decile of the burst. During FC, recruitment times did not change compared with control, although the duration of the phrenic burst doubled. Discharge frequencies increased and recruitment order of phrenic motoneurons was virtually unaffected during FC and FV. Limited recruitment of previously inactive neurons in the filaments from which we recorded was found during FV and FC. During FV, 1 previously inactive motoneuron was recruited in 16 filaments containing 25 spontaneously active motor axons. During FC, 3 new motoneurons were recruited in addition to the 64 already active in 35 filaments. Recruitment during FV and FC was absent even when recording from filaments known, on the basis of antidromic activation, to contain inactive motor axons. During FV, 10 of 26 motoneurons began their discharges with doublets (interspike interval < 10 ms); doublets occurred in only 4 of 67 motoneurons during FC. Already active phrenic motoneurons contributed to the intense phrenic activity associated with both respiratory (coughing) and nonrespiratory (vomiting) behavior by increases in discharge frequency, earlier recruitment, and doublets; the contribution of previously quiescent motoneurons remains uncertain.     

Attenuation of phrenic motor discharge by phrenic nerve afferents

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

Analysis of postinspiratory activity of phrenic motoneurons with chemical and vagal reflexes

We examined the effects of chemical and reflex drives on the postinspiratory inspiratory activity (PIIA) of phrenic motoneurons using a single-fiber technique. Action potentials from "single" fibers were recorded from the C5 phrenic root together with contralateral mass phrenic activity (also from C5) in anesthetized, paralyzed, and artificially ventilated cats with intact vagus and carotid sinus nerves. Nerve fibers were classified as "early" or "late" based on their onset of discharge in relation to mass phrenic activity during hyperoxic ventilation. Only the early fibers displayed PIIA but not the late fibers, even when their activity began earlier in inspiration with increased chemical drives. Isocapnic hypoxia increased, whereas hyperoxic hypercapnia shortened the duration of PIIA. Pulmonary stretch and "irritant" receptors inhibited PIIA. Hypercapnia and stimulation of peripheral chemoreceptors by lobeline excited both early and late units to the same extent, but hypoxic ventilation had a less marked excitatory effect on late fiber activity. Irritant receptor activation increased the activity of early more than late fibers. Hyperoxic hyperventilation eliminated late phrenic fiber activity, whereas early fibers became tonically active. Bilateral vagotomy abolished this sustained discharge in eight of nine early units, suggesting the importance of vagal afferents in producing tonic firing during hyperventilation. These results suggest that early and late phrenic fibers have different responses to chemical stimuli and to vagally mediated reflexes; late units do not discharge in postinspiratory period, whereas early fibers do; the PIIA is not affected in the same way by various chemical and vagal inputs; and early units that exhibit PIIA display tonic activity with hyperoxic hypocapnia.     

Responses of pulmonary stretch receptors during ramp inflations of the lung

Studies were conducted in anesthetized paralyzed dogs to determine how the dynamic and proportional sensitivity of pulmonary stretch receptors change during lung inflation. The firing of each receptor was examined at multiple levels of static transpulmonary pressure and during multiple identical inflations at each of several rates. The averaged response of the receptor was computed and receptor activity related to transpulmonary pressure. On the basis of a quantitative criterion, employed to distinguish type I from type II receptors, the receptors could not be divided into distinct subpopulations. Thus all receptors were treated as coming from a single population. For all receptors we observed that their proportional sensitivity (increases in firing produced by increases in lung expansion at a constant rate of inflation) declined as the lung was inflated. In contrast, the dynamic sensitivity (increases in firing produced by increased rates of inflation at constant transpulmonary pressure) increased or remained relatively constant with increasing lung expansion. Thus, as inflation volume increases, the pulmonary stretch receptor acts increasingly as a rate receptor. The rate of inflation may have a more important role in control of the inspiratory duration than previously realized.     

Responses of single phrenic motoneurons to altered ventilatory drives in anesthetized dogs

We studied the effects of altered ventilatory drives on the activity of the whole phrenic nerve and single phrenic motoneurons in dogs anesthetized with alpha-chloralose and paralyzed with gallamine triethiodide. Single phrenic motoneurons were classified as either late-onset or early-onset motoneurons (LOM and EOM, respectively), depending on the time of onset of their activity during inspiration. Increase in ventilatory drive was induced by altering chemical drive with changes in arterial blood gases and also by altering the vagal afferent contribution to ventilatory drive. The latter was accomplished by inducing pulmonary gas embolism (PGE) during hyperoxia. Whole phrenic nerve activity was increased by both types of increase in ventilatory drive. In both cases, changes in the firing pattern of LOMs and EOMs were responsible for the increased phrenic output. The changes in post-PGE firing pattern of the LOMs generally consisted of a shift in the time of onset to an earlier point in inspiration and an increase in the number of spikes per inspiratory cycle. Vagotomy abolished the difference between the contributions of LOMs and EOMs to the phrenic response to PGE. Data from dogs studied while they were breathing spontaneously were qualitatively the same as those from the paralyzed animals, indicating no major role for phasic volume feedback in these responses. Our data regarding altered chemical drive are similar to those reported earlier in other species, whereas those regarding PGE demonstrate that vagally mediated increases in ventilatory drive affect both LOMs and EOMs, although LOMs are affected to a greater degree.(ABSTRACT TRUNCATED AT 250 WORDS)     

Short-term plasticity of descending synaptic input to phrenic motoneurons in rats.

Respiratory afferent stimulation can elicit increases in respiratory motor output that outlast the period of stimulation by seconds to minutes [short-term potentiation (STP)]. This study examined the potential contribution of spinal mechanisms to STP in anesthetized, vagotomized, paralyzed rats. After C(1) spinal cord transection, stimulus trains (100 Hz, 5-60 s) of the C(1)-C(2) lateral funiculus elicited STP of phrenic nerve activity that peaked several seconds poststimulation. Intracellular recording revealed that individual phrenic motoneurons exhibited one of three different responses to stimulation: 1) depolarization that peaked several seconds poststimulation, 2) depolarization during stimulation and then exponential repolarization after stimulation, and 3) bistable behavior in which motoneurons depolarized to a new, relatively stable level that was maintained after stimulus termination. During the STP, excitatory postsynaptic potentials elicited by single-stimulus pulses were larger and longer. In conclusion, repetitive activation of the descending inputs to phrenic motoneurons causes a short-lasting depolarization of phrenic motoneurons, and augmentation of excitatory postsynaptic potentials, consistent with a contribution to STP.     

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.     

Statistical inference on spontaneous neuronal discharge patterns

A statistical analysis was performed on extracellularly recorded spike trains of spontaneously active mesencephalic reticular neurons of rats. Only stationary records were used for detailed examination. The moments of interspike intervals were computed, hypothesis of renewal process and its specific forms was tested. Implications for statistical methodology are considered on the basis of the results. The main emphasis is laid on the connection between experimental results and stochastic neuronal models.     

Influence of phasic afferent information on phrenic neural output during hypercapnia

We measured the moving time average (MTA) of the phrenic neurogram before and after removal of phasic afferent information from the lungs, chest wall, and oscillations in blood gases by using constant-flow ventilation (CFV). Anesthetized dogs were studied at various levels of steady-state and progressive hypercapnia during spontaneous breathing and during CFV. When steady-state and progressive hypercapnia were compared, the frequency and height of the MTA phrenic neurogram were independent of the rate of induction of hypercapnia during each mode of ventilation. During spontaneous ventilation, the response to hypercapnia comprised mainly an increase in frequency with only a slight increase in the amplitude of the MTA phrenic waveform. During muscular paralysis and CFV, the responses were similar to those observed after vagotomy with mainly an increase in the amplitude and only a small increase in frequency. For both spontaneous breathing and CFV, increases in frequency were achieved mainly by a shortening in expiratory time with the inspiratory time remaining relatively constant. Our data support the concept of a centrally patterned respiratory generator, whose inherent pattern is modified by phasic feedback from peripheral receptors mainly of vagal origin.     

Activity patterns of cardiac vagal motoneurons in rat nucleus ambiguus

Extracellular recordings were made in the right nucleus ambiguus of urethane-anesthetized rats from 33 neurons that were activated at constant latency from the craniovagal cardiac branch. Their calculated conduction velocities were in the B-fiber range (1.6-13.8 m/s, median 4.2), and most (22/33) were silent. Active units were confirmed as cardiac vagal motoneurons (CVM) by the collision test for antidromic activation and by the presence of cardiac rhythmicity in their resting discharge (9/9). Brief arterial pressure rises of 20-50 mmHg increased the activity in five of five CVM by 0.1 +/- 0.02 spikes. s(-1). mmHg(-1) from a resting 3.8 +/- 1.2 spikes/s; they also recruited activity in two of four previously silent cardiac branch-projecting neurons. CVM firing was modulated by the central respiratory cycle, showing peak activity during inspiration (8/8). Rat CVM thus show firing properties similar to those in other species, but their respiratory pattern is distinct. These findings are discussed in relation to mechanisms of respiratory sinus arrhythmia.     

Influence of forelimb afferents on the activity of lumbar spinal-cord motoneurons

Experiments were conducted on anesthetized cats with microelectrode recording to study the synaptic responses that develop in the lumbar motoneurons on stimulation of the afferent fibers of groups II and III in the nerves of the ipsilateral and contralateral forelegs. Stimulation of these afferents evoked predominantly inhibitory postsynaptic potentials (IPSP) in the extensor motoneurons and excitatory postsynaptic potentials (EPSP) in the flexor motoneurons. A basically inhibitory change in the rhythmic background activity developed under the influence of descending impulsation. The duration of the total inhibition of "spontaneous" motoneuron activity corresponded to the duration of the inhibitory influences exerted by the forelimb flexor-reflex afferents (FRA) on the interneurons. The interaction of the descending and segmental PSP resulted in inhibition and facilitation of the segmental responses in the motoneurons. The ultimate result of this interaction was determined by the shifts in the membrane potential of the motoneuron and by the effects created in the interneurons.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 3, No. 1, pp. 58–67, January–February, 1971.