Comparison of phrenic motoneuron responses to hypercapnia and isocapnic hypoxia

1979 ◽  
Vol 46 (6) ◽  
pp. 1096-1102 ◽  
Author(s):  
W. M. St John ◽  
D. Bartlett

This study was undertaken to compare phrenic motoneuron responses to hypercapnia and isocapnic hypoxia. Efferent activity of single phrenic nerve fibers was recorded with that of the contralateral phrenic nerve in decerebrate cats which were vagotomized, paralyzed, and artificially ventilated. At normocapnia in hyperoxia, single phrenic fibers were distributed into approximately equal “early” and “late” populations according to their onset of activity relative to the period of the phrenic burst. Elevations of PACO2 or diminutions of PAO2 resulted in progressive increases in the number of spikes per respiratory cycle and decreases in the modal interspike interval for both early and late units. Moreover, either stimulus caused an onset of late unit activity at progressively earlier portions of inspiration. At equivalent levels of peak integrated phrenic discharge achieved at normocapnia or hypercapnia as compared to normoxia or hypoxia, there were no differences in activity patterns for either early or late units. It is concluded that hypoxia-induced alterations in the activity of single phrenic motoneurons are identical to those changes resulting from hypercapnia.


1994 ◽  
Vol 77 (2) ◽  
pp. 679-683 ◽  
Author(s):  
Y. Nakazono ◽  
M. Aoki

This study aimed to determine whether upper cervical inspiratory neurons (UCINs), which are localized in the intermediolateral part of the gray matter of the upper cervical segments, have propriospinal connections to phrenic motoneurons of the ipsilateral lower cervical segment in anesthetized cats. Unit action potentials of UCINs were extracellularly recorded simultaneously with ipsilateral phrenic nerve activity. To eliminate the descending influences from medullary respiratory neurons to phrenic motoneurons, bulbospinal conduction paths were temporarily blocked by focal cooling applied to the ventral caudal medulla at the pyramidal decussation level by means of a cooling thermode (1 mm tip diam). By using a spike-triggered method, during cooling phrenic nerve activities were evoked by UCIN spikes that were elicited by microinjection of L-glutamate for 20 of the 55 (36%) UCIN units examined. The onset latencies of these phrenic motoneuron responses ranged from 1.5 to 7.1 ms (mean 3.6 ms), depending on synaptic transmission delays. These results clearly demonstrate that UCINs have, at least in part, excitatory mono- and paucisynaptic connections with ipsilateral phrenic motoneurons.



2009 ◽  
Vol 102 (4) ◽  
pp. 2184-2193 ◽  
Author(s):  
Kun-Ze Lee ◽  
Paul J. Reier ◽  
David D. Fuller

Hypoxia-induced short-term potentiation (STP) of respiratory motor output is manifested by a progressive increase in activity after the acute hypoxic response and a gradual decrease in activity on termination of hypoxia. We hypothesized that STP would be differentially expressed between physiologically defined phrenic motoneurons (PhrMNs). Phrenic nerve “single fiber” recordings were used to characterize PhrMN discharge in anesthetized, vagotomized and ventilated rats. PhrMNs were classified as early (Early-I) or late inspiratory (Late-I) according to burst onset relative to the contralateral phrenic neurogram during normocapnic baseline conditions. During hypoxia (FIO2 = 0.12–0.14, 3 min), both Early-I and Late-I PhrMNs abruptly increased discharge frequency. Both cell types also showed a progressive increase in frequency over the remainder of hypoxia. However, Early-I PhrMNs showed reduced overall discharge duration and total spikes/breath during hypoxia, whereas Late-I PhrMNs maintained constant discharge duration and therefore increased the number of spikes/breath. A population of previously inactive (i.e., silent) PhrMNs was recruited 48 ± 8 s after hypoxia onset. These PhrMNs had a Late-I onset, and the majority (8/9) ceased bursting promptly on termination of hypoxia. In contrast, both Early-I and Late-I PhrMNs showed post-hypoxia STP as reflected by greater discharge frequencies and spikes/breath during the post-hypoxic period ( P < 0.01 vs. baseline). We conclude that the expression of phrenic STP during hypoxia reflects increased activity in previously active Early-I and Late-I PhrMNs and recruitment of silent PhrMNs. post-hypoxia STP primarily reflects persistent increases in the discharge of PhrMNs, which were active before hypoxia.



1983 ◽  
Vol 55 (3) ◽  
pp. 793-798 ◽  
Author(s):  
J. C. Hwang ◽  
D. Bartlett ◽  
W. M. St John

In decerebrate, vagotomized, paralyzed, and ventilated cats, activities of the phrenic nerve and single hypoglossal nerve fibers were monitored. The great majority of hypoglossal neuronal activities were inspiratory (I), discharging during a period approximating that of phrenic. Many were not active at normocapnia but were recruited in hypercapnia or hypoxia. Once recruited, discharge frequencies, which rose quickly to near maximal levels in early to midinspiration, significantly increased with further augmentations of drive. Also, the onset of activities became progressively earlier, compared with phrenic discharge, in hypercapnia or hypoxia. Smaller numbers of hypoglossal fiber activities, having inspiratory-expiratory (I-E), expiratory (E), expiratory-inspiratory (E-I), or tonic discharge patterns, were also recorded. Activities of E, I-E, and those I fibers that became I-E in high drive may underlie the early burst of expiratory activity of the hypoglossal nerve. It is concluded that the firing and recruitment patterns of hypoglossal neurons differ from those of phrenic motoneurons. However, responses to chemoreceptor stimuli are similar among the two neuronal groups.



1992 ◽  
Vol 73 (4) ◽  
pp. 1626-1636 ◽  
Author(s):  
S. Milano ◽  
L. Grelot ◽  
A. L. Bianchi ◽  
S. Iscoe

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.



1995 ◽  
Vol 268 (6) ◽  
pp. R1381-R1385 ◽  
Author(s):  
B. J. Yates ◽  
M. S. Siniaia ◽  
A. D. Miller

The objective of this study was to determine which brain stem regions that have projections to sympathetic preganglionic neurons or phrenic motoneurons ae necessary for vestibulosympathetic or vestibulorespiratory responses in decerebrate cats. Bilateral kainic acid injections into the rostral ventrolateral medulla abolished splanchnic nerve responses to electrical stimulation of the vestibular nerve, suggesting that this region is critical for the production of vestibulosympathetic responses. In contrast, injections into the caudal medullary raphe nuclei had no apparent effect on the responses. Neither the dorsal nor the ventral respiratory group appears to be necessary for mediating vestibular influences on the phrenic nerve, suggesting that nonrespiratory neurons (such as vestibulospinal neurons) may be important for producing vestibulorespiratory responses.



1996 ◽  
Vol 81 (5) ◽  
pp. 2260-2266 ◽  
Author(s):  
Steve Iscoe

Iscoe, Steve. Phrenic motoneuron discharge during sustained inspiratory resistive loading. J. Appl. Physiol. 81(5): 2260–2266, 1996.—I determined whether prolonged inspiratory resistive loading (IRL) affects phrenic motoneuron discharge, independent of changes in chemical drive. In seven decerebrate spontaneously breathing cats, the discharge patterns of eight phrenic motoneurons from filaments of one phrenic nerve were monitored, along with the global activity of the contralateral phrenic nerve, transdiaphragmatic pressure, and fractional end-tidal CO2 levels. Discharge patterns during hyperoxic CO2 rebreathing and breathing against an IRL (2,500–4,000 cmH2O ⋅ l−1 ⋅ s) were compared. During IRL, transdiaphragmatic pressure increased and then either plateaued or decreased. At the highest fractional end-tidal CO2 common to both runs, instantaneous discharge frequencies in six motoneurons were greater during sustained IRL than during rebreathing, when compared at the same time after the onset of inspiration. These increased discharge frequencies suggest the presence of a load-induced nonchemical drive to phrenic motoneurons from unidentified source(s).



1981 ◽  
Vol 50 (5) ◽  
pp. 994-998 ◽  
Author(s):  
W. M. St John ◽  
D. Bartlett

Single-fiber phrenic nerve action potentials were recorded together with activity of contralateral whole phrenic nerve rootlets during eupnea and gasping in decerebrate, cerebellectomized, vagotomized, paralyzed, and ventilated cats. Gasping was reversibly produced by cooling a fork thermode positioned through the pontomedullary junction. In eupnea, phrenic motoneurons were distributed into "early" and "late" populations relative to their onset of activity during inspiration. During gasping, however, both fiber types typically commenced activity at the beginning of the phrenic nerve burst. Moreover, late fibers, but not early units, exhibited an augmentation of discharge frequency with the onset of gasping. The concentration of activity of all phrenic motoneurons at the beginning of inspiration and the increase in late-unit discharge frequency account for the faster rise of the gasp as compared with the eupneic breath. It is concluded that the pattern of phrenic nerve activation during gasping differs fundamentally from that during eupnea. These results support the concept that mechanisms underlying the neurogenesis of gasping and eupnea may not be identical.



1989 ◽  
Vol 67 (4) ◽  
pp. 1364-1370 ◽  
Author(s):  
D. F. Speck

Neuronal recordings, microstimulation, and electrolytic and chemical lesions were used to examine the involvement of the Botzinger Complex (BotC) in the bilateral phrenic-to-phrenic inhibitory reflex. Experiments were conducted in decerebrate cats that were paralyzed, ventilated, thoracotomized, and vagotomized. Microelectrode recordings within the BotC region revealed that some neurons were activated by phrenic nerve stimulation (15 of 69 expiratory units, 9 of 67 inspiratory units, and 19 nonrespiratory-modulated units) at average latencies similar to the onset latency of the phrenic-to-phrenic inhibition. In addition, microstimulation within the BotC caused a short latency transient inhibition of phrenic motor activity. In 17 cats phrenic neurogram responses to threshold and supramaximal (15 mA) stimulation of phrenic nerve afferents were recorded before and after electrolytic BotC lesions. In 15 animals the inhibitory reflex was attenuated by bilateral lesions. Because lesion of either BotC neurons or axons of passage could account for this attenuation, in eight experiments the phrenic-to-phrenic inhibitory responses were recorded before and after bilateral injections of 5 microM kainic acid (30–150 nl) into the BotC. After chemical lesions, the inhibitory response to phrenic nerve stimulation remained; however, neuronal activity typical of the BotC could not be located. These results suggest that axons important in producing the phrenic-to-phrenic reflex pass through the region of the BotC, but that BotC neurons themselves are not necessary for this reflex.



1976 ◽  
Vol 231 (4) ◽  
pp. 1033-1038 ◽  
Author(s):  
GM Schoepfle

Repetitive stimulation of a single medullated nerve fiber of Xenopus yields a succession of postspike voltage-time curves which are nearly coincident until attainment of a voltage that corresponds to that of the maximum attained by the normal postspike undershoot. Initially the interspike potential returns toward a resting level after this brief phase of hyperpolarization. However, as tetanization proceeds, a pattern of hyperpolarization develops with the result that, in the tetanic steady state, there exists a progressive hyperpolarization throughout each interspike interval. Extent of postspike hyperpolarization in terms of a deviation deltaVm from the resting level of membrane potential is approximated by the variation deltaVm = delta[MNa + MK]/[GNa + GK] where MNa and MK are current densities associated with active pumping of sodium and potassium ions and GNa and GK are corresponding time-dependent leak conductances. Tetanic hyperpolarization is reversibly abolished by cyanide and by exposure to lithium Ringer. Eventual reappearance of tetanic hyperpolarization in the presence of lithium Ringer suggests lithium pumping.



Author(s):  
Raphael Rodrigues Perim ◽  
Michael D. Sunshine ◽  
Joseph F. Welch ◽  
Juliet Santiago ◽  
Ashley Holland ◽  
...  

Plasticity is a hallmark of the respiratory neural control system. Phrenic long-term facilitation (pLTF) is one form of respiratory plasticity characterized by persistent increases in phrenic nerve activity following acute intermittent hypoxia (AIH). Although there is evidence that key steps in the cellular pathway giving rise to pLTF are localized within phrenic motor neurons (PMNs), the impact of AIH on the strength of breathing-related synaptic inputs to PMNs remains unclear. Further, the functional impact of AIH is enhanced by repeated/daily exposure to AIH (dAIH). Here, we explored the effects of AIH vs. 2 weeks of dAIH preconditioning on spontaneous and evoked responses recorded in anesthetized, paralyzed (with pancuronium bromide) and mechanically ventilated rats. Evoked phrenic potentials were elicited by respiratory cycle-triggered lateral funiculus stimulation at C2 delivered prior to- and 60 min post-AIH (or an equivalent time in controls). Charge-balanced biphasic pulses (100 µs/phase) of progressively increasing intensity (100 to 700 µA) were delivered during the inspiratory and expiratory phases of the respiratory cycle. Although robust pLTF (~60% from baseline) was observed after a single exposure to moderate AIH (3 x 5 min; 5 min intervals), there was no effect on evoked phrenic responses, contrary to our initial hypothesis. However, in rats preconditioned with dAIH, baseline phrenic nerve activity and evoked responses were increased, suggesting that repeated exposure to AIH enhances functional synaptic strength when assessed using this technique. The impact of daily AIH preconditioning on synaptic inputs to PMNs raises interesting questions that require further exploration.



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