Midcervical neuronal discharge patterns during and following hypoxia

Anatomical evidence indicates that midcervical interneurons can be synaptically coupled with phrenic motoneurons. Accordingly, we hypothesized that interneurons in the C3–C4 spinal cord can display discharge patterns temporally linked with inspiratory phrenic motor output. Anesthetized adult rats were studied before, during, and after a 4-min bout of moderate hypoxia. Neuronal discharge in C3–C4 lamina I–IX was monitored using a multielectrode array while phrenic nerve activity was extracellularly recorded. For the majority of cells, spike-triggered averaging (STA) of ipsilateral inspiratory phrenic nerve activity based on neuronal discharge provided no evidence of discharge synchrony. However, a distinct STA phrenic peak with a 6.83 ± 1.1 ms lag was present for 5% of neurons, a result that indicates a monosynaptic connection with phrenic motoneurons. The majority (93%) of neurons changed discharge rate during hypoxia, and the diverse responses included both increased and decreased firing. Hypoxia did not change the incidence of STA peaks in the phrenic nerve signal. Following hypoxia, 40% of neurons continued to discharge at rates above prehypoxia values (i.e., short-term potentiation, STP), and cells with initially low discharge rates were more likely to show STP ( P < 0.001). We conclude that a population of nonphrenic C3–C4 neurons in the rat spinal cord is synaptically coupled to the phrenic motoneuron pool, and these cells can modulate inspiratory phrenic output. In addition, the C3–C4 propriospinal network shows a robust and complex pattern of activation both during and following an acute bout of hypoxia.

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Synaptic Inhibition of Cat Phrenic Motoneurons by Internal Intercostal Nerve Stimulation

Journal of Neurophysiology ◽

10.1152/jn.1999.82.3.1224 ◽

1999 ◽

Vol 82 (3) ◽

pp. 1224-1232 ◽

Cited By ~ 34

Author(s):

Mark C. Bellingham

Keyword(s):

Phrenic Nerve ◽

Intercostal Nerve ◽

Evoked Responses ◽

Nerve Activity ◽

Synaptic Inputs ◽

Phrenic Nerve Activity ◽

Reflex Pathways ◽

Phrenic Motoneurons ◽

Conditioning Stimuli ◽

Stimulation Of

Intracellular recordings from 65 phrenic motoneurons (PMNs) in the C5 segment and recordings of C5 phrenic nerve activity were made in 27 pentobarbitone-anesthetized, paralyzed, and artificially ventilated adult cats. Inhibition of phrenic nerve activity and PMN membrane potential hyperpolarization (48/55 PMNs tested) was seen after stimulation of the internal intercostal nerve (IIN) at a mean latency to onset of 10.3 ± 2.7 ms. Reversal of IIN-evoked hyperpolarization ( n = 14) by injection of negative current or diffusion of chloride ions occurred in six cases, and the hyperpolarization was reduced in seven others. Stimulation of the IIN thus activates chloride-dependent inhibitory synaptic inputs to most PMNs. The inhibitory phrenic nerve response to IIN stimulation was reduced by ipsilateral transection of the lateral white matter at the C3 level and was converted to an excitatory response by complete ipsilateral cord hemisection at the same level. After complete ipsilateral hemisection of the spinal cord at C3 level, stimulation of the IIN evoked both excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in PMNs ( n = 10). It was concluded that IIN stimulation can evoke both excitatory and inhibitory responses in PMNs using purely spinal circuitry, but that excitatory responses are normally suppressed by a descending pathway in intact animals. Fifteen PMNs were tested for possible presynaptic convergence of inputs in these reflex pathways, using test and conditioning stimuli. Significant enhancement (>20%) of IPSPs were seen in seven of eight IIN-evoked responses using pericruciate sensorimotor cortex (SMC) conditioning stimuli, but only one of five IIN-evoked responses were enhanced by superior laryngeal nerve (SLN) conditioning stimuli. The IIN-evoked IPSP was enhanced in one of two motoneurons by stimulation of the contralateral phrenic nerve. It was concluded that presynaptic interneurons were shared by the IIN and SMC pathways, but uncommonly by other pathways. These results indicate that PMNs receive inhibitory synaptic inputs from ascending thoracocervical pathways and from spinal interneurons. These inhibitory reflex pathways activated by afferent inputs from the chest wall may play a significant role in the control of PMN discharge, in parallel with disfacilitation following reduced activity in bulbospinal neurons projecting to PMNs.

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Effects of Serotonin on Crossed Phrenic Nerve Activity in Cervical Spinal Cord Hemisected Rats

Experimental Neurology ◽

10.1006/exnr.1999.7213 ◽

1999 ◽

Vol 160 (2) ◽

pp. 446-453 ◽

Cited By ~ 26

Author(s):

Shi-Yi Zhou ◽

Harry G. Goshgarian

Keyword(s):

Spinal Cord ◽

Phrenic Nerve ◽

Cervical Spinal Cord ◽

Nerve Activity ◽

Phrenic Nerve Activity

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Cervical spinal demyelination with ethidium bromide reversibly impairs phrenic nerve activity in adult rats

The FASEB Journal ◽

10.1096/fasebj.26.1_supplement.704.7 ◽

2012 ◽

Vol 26 (S1) ◽

Author(s):

Rebecca A. Johnson ◽

Nicole L. Nichols ◽

Ian D. Duncan ◽

Antonio M. Punzo ◽

Gordon S. Mitchell

Keyword(s):

Ethidium Bromide ◽

Phrenic Nerve ◽

Nerve Activity ◽

Adult Rats ◽

Phrenic Nerve Activity

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Serotonin2 receptors mediate respiratory recovery after cervical spinal cord hemisection in adult rats

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.6.2665 ◽

2001 ◽

Vol 91 (6) ◽

pp. 2665-2673 ◽

Cited By ~ 46

Author(s):

Shi-Yi Zhou ◽

Gregory J. Basura ◽

Harry G. Goshgarian

Keyword(s):

Spinal Cord ◽

Receptor Antagonist ◽

Phrenic Nerve ◽

Cervical Spinal Cord ◽

Sprague Dawley ◽

Related Activity ◽

Adult Rats ◽

Cord Injury ◽

Respiratory Recovery ◽

Spinal Cord Hemisection

The aim of the present study was to specifically investigate the involvement of serotonin [5-hydroxytryptamine (5-HT2)] receptors in 5-HT-mediated respiratory recovery after cervical hemisection. Experiments were conducted on C2 spinal cord-hemisected, anesthetized (chloral hydrate, 400 mg/kg ip), vagotomized, pancuronium- paralyzed, and artificially ventilated female Sprague-Dawley rats in which CO2 levels were monitored and maintained. Twenty-four hours after spinal hemisection, the ipsilateral phrenic nerve displayed no respiratory-related activity indicative of a functionally complete hemisection. Intravenous administration of the 5-HT2A/2C-receptor agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) induced respiratory-related activity in the phrenic nerve ipsilateral to hemisection under conditions in which CO2 was maintained at constant levels and augmented the activity induced under conditions of hypercapnia. The effects of DOI were found to be dose dependent, and the recovery of activity could be maintained for up to 2 h after a single injection. DOI-induced recovery was attenuated by the 5-HT2-receptor antagonist ketanserin but not with the 5-HT2C-receptor antagonist RS-102221, suggesting that 5-HT2A and not necessarily 5-HT2C receptors may be involved in the induction of respiratory recovery after cervical spinal cord injury.

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Microinjections of glycine into the pre-Bötzinger complex inhibit phrenic nerve activity in the rat

Brain Research ◽

10.1016/s0006-8993(02)02902-5 ◽

2002 ◽

Vol 947 (1) ◽

pp. 25-33 ◽

Cited By ~ 7

Author(s):

V.C Chitravanshi ◽

H.N Sapru

Keyword(s):

Phrenic Nerve ◽

Nerve Activity ◽

Phrenic Nerve Activity ◽

Bötzinger Complex

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Daily acute intermittent hypoxia enhances phrenic motor output and stimulus-evoked phrenic responses in rats

Journal of Neurophysiology ◽

10.1152/jn.00112.2021 ◽

2021 ◽

Author(s):

Raphael Rodrigues Perim ◽

Michael D. Sunshine ◽

Joseph F. Welch ◽

Juliet Santiago ◽

Ashley Holland ◽

...

Keyword(s):

Motor Neurons ◽

Phrenic Nerve ◽

Intermittent Hypoxia ◽

Neural Control ◽

Respiratory Cycle ◽

Evoked Responses ◽

Nerve Activity ◽

Synaptic Inputs ◽

Phrenic Nerve Activity ◽

The Impact

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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Evaluation of a New Valveless all Purpose Ventilator: Effect of Ventilating Frequency PEEP, PACO2 and PAO2 on Phrenic Nerve Activity

Perspectives in High Frequency Ventilation - Developments in Critical Care Medicine and Anesthesiology ◽

10.1007/978-94-009-6711-3_15 ◽

1983 ◽

pp. 140-145 ◽

Cited By ~ 2

Author(s):

M. K. Chakrabarti ◽

J. G. Whitwam

Keyword(s):

Phrenic Nerve ◽

Nerve Activity ◽

Phrenic Nerve Activity

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Effects of hypercapnia and hypoxia on phrenic nerve activity and respiratory timing

Journal of Applied Physiology ◽

10.1152/jappl.1981.51.3.732 ◽

1981 ◽

Vol 51 (3) ◽

pp. 732-738 ◽

Cited By ~ 18

Author(s):

J. F. Ledlie ◽

S. G. Kelsen ◽

N. S. Cherniack ◽

A. P. Fishman

Keyword(s):

Phrenic Nerve ◽

Carotid Sinus ◽

Peak Height ◽

Inspiratory Time ◽

Nerve Activity ◽

Phrenic Nerve Activity ◽

Chemical Stimuli ◽

Proprioceptive Inputs ◽

Spontaneously Breathing ◽

Respiratory Responses

In the spontaneously breathing animal, respiratory responses to chemical stimuli are influenced by phasic proprioceptive inputs from the thorax. We have compared the effects of hypercapnia and hypoxia on the level and timing of phrenic nerve activity while these phasic afferent signals were absent. Progressive hyperoxic hypercapnia and isocapnic hypoxia were produced in anesthetized paralyzed dogs by allowing 3–5 min of apnea to follow mechanical ventilation with 100% O2 or 35% O2 in N2, respectively; during hypoxia, isocapnia was maintained by intravenous infusion of tris(hydroxymethyl)aminomethane buffer. The peak height (P) of nerve bursts, inspiratory time (TI), and expiratory time (TE) were measured from the phrenic neurogram. With the vagi intact or severed, hypoxia decreased TI, whereas hypercapnia did not; both stimuli decreased TE. At the same minute phrenic activity (P x frequency), P, TI, and TE were all less during hypoxia than during hypercapnia. The decreases in TI and TE with hypoxia were significantly less after carotid sinus denervation. The results indicate that the patterns of phrenic nerve activity in response to hypoxia and hypercapnia are different: hypoxia has a greater effect on respiratory timing, whereas hypercapnia has a greater effect on peak phrenic nerve activity. The effect of hypoxia on respiratory timing is largely mediated by the peripheral chemoreceptors.

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