Phrenic reflexes in the decerebrate and spinal rabbit

Investigations were undertaken to study the characteristics of phrenic reflexes with partial or total elimination of the descending neuronal pathways. Experiments were performed on 17 decerebrate, vagotomized, paralysed and artificially ventilated rabbits. The experimental procedure included a midsagittal section of the medulla or a hemisection followed by a total transection of the spinal cord at C1. The effects of compression of the rostral or caudal parts of the thorax, pressure on the muscles at the lumbar level and passive movements of the hindlimb were studied on the efferent vagal and phrenic neurograms. Partial elimination of the descending pathways evoked an increase in the intensity of the spinal reflexes. Characteristics of the reflexes which we have obtained after lesions of the medulla or spinal cord enable us to search for their central path. After transection of the spinal cord, no sustained phasic phrenic nerve activities were observed. The results suggest that after high cordotomy the phrenic motoneuronal pool has a potential capability for generating phasic bursts and additional inputs are required for their development.     

脊髓休克期大鼠迷走神经、膈神经和主动脉神经放电的动态变化

目的：寻找大鼠颈髓横断（CSCT）后脊髓休克期间迷走神经、膈神经和主动脉神经放电的动态变化规律。方法：将50只SD大鼠随机平均分为5组（n=10）：假手术组（A组）、CSCT后0~3h组（B组）、3~6h组（C组）、6~9h组（D组）、9~12h组（E组）。在C7~T1节段完全切断脊髓,建立颈脊髓横断模型,用电生理技术同步记录迷走神经、膈神经和主动脉神经放电、动脉血压和呼吸流量。结果：迷走神经、膈神经和主动脉神经放电呈群集性。B、C、D组迷走神经、膈神经放电周期延长、群集内放电增强、呼吸流量增加,与A组比较,差异有统计学意义（P〈0.05）,其中C组群集内放电最强。B、C、D、E组主动脉神经放电周期延长、群集内放电减弱,B、C、D组的平均动脉压降低,与A组比较,差异有统计学意义（P〈0.05）,其中B、C组主动脉神经群集内放电最弱,平均动脉压最低（P〈0.05）。结论：大鼠颈脊髓横断后,在脊髓休克期间迷走神经、膈神经群集放电活动增强,主动脉神经群集放电减弱,其动态变化与呼吸循环功能的改变有关。     

Foreword

High frequency spinal cord stimulation (HF-SCS) is a method of inspiratory muscle activation resulting in phrenic motoneuron activation via stimulation of spinal cord pathways. The specific pathways mediating this response, however, are unknown. The aim of this study was to assess the potential role of upper cervical (C1–C4) pre-phrenic interneurons (UCI) and localize the pathways in the thoracic spinal cord mediating activation of phrenic motoneurons during HF-SCS. In 7 anesthetized, spinalized (C1 level) dogs, HF-SCS was applied at the T2 level. Diaphragm EMG, inspired volume and airway pressure generation were monitored before and following sequential spinal cord sections at the C4 and C8 levels. Section at the C4 level and dorsal columns at C8 resulted in no significant changes. However, lateral funiculi section (C8 level) resulted in significant reductions in each parameter. We conclude that during upper thoracic HF-SCS, the phrenic motoneuron pools are activated via spinal pathways located in the lateral funiculus but UCI are not involved.     

Evidence for respiratory and locomotor pattern generators in the rabbit cervico-thoracic cord and for their interactions

In addition to the wellknown fictive locomotion, a fictive respiration can also be obtained in decorticate, unanaesthetized rabbit preparations after curarization and vagotomy. Both patterns were abolished after high spinal (C2 or C3) transection. Spinal rhythmic capabilities could be disclosed after administration of nialamide and DOPA: together with the earlier demonstrated locomotor-like bursting in hindlimb and forelimb muscle nerves, two different types of phrenic bursting patterns could be observed, depending on endtidal CO2 levels: (1) short lasting phrenic bursts (SLPBs), coordinated with locomotor bursts, result of a locomotor driving process; (2) when end-tidal CO2 was slightly increased (4.5 instead of 4.0%), long lasting phrenic bursts (LLPBs) developed: they have no causal link with the locomotor bursts. Intraspinal interactions were shown to operate between these rhythmic patterns: (1) the already mentioned caudo-rostral driving from hindlimb or posterior locomotion generators (pLGs) onto forelimb bursting and onto phrenic activity too (providing SLPBs in the latter case); (2) the rostro-caudal inhibition of fore- and hindlimb locomotor activity throughout each LLPB. Since forelimb locomotor-like bursting and LLPBs could still be obtained after functional isolation of the cervico-thoracic cord (through C2 and Th12 spinal transections) with comparable interactions as before Th12 transection, it is concluded that: two categories of generators, forelimb or anterior locomotion generators (aLGs), and chemosensitive respiration generators (RGs) are both present in this part of the cord, on the one hand; interactions between RGs and pLGs are likely to be achieved via aLGs on the other.     

Motoneuron response to dorsal root stimulation in anesthetized monkeys after spinal cord transection

Summary In preparation for studying the spinal cord alterations produced by operant conditioning of spinal reflexes, we studied peripheral nerve responses to supramaximal dorsal root stimulation in the lumbosacral cord of deeply anesthetized monkeys before and after thoracic cord transection. Except for variable depression in the first few minutes, reflex responses were not reduced or otherwise significantly affected by transection in the hour immediately following the lesion or for at least 50 h. The results suggest that reduction in muscle spindle sensitivity and/or in polysynaptic motoneuron excitation contributes to stretch reflex depression after cord transection.     

Coordinated rhythmic bursting in respiratory and locomotor muscle nerves in the spinal rabbit.

In unanaesthetized, curarized spinal rabbits (C2 level) treated with Niamide and DOPA, rhythmic activities were recorded from the phrenic nerves; close coordination was observed between the phrenic bursts and the locomotor bursts which developed in hindlimb muscle nerves. The frequency of phrenic bursts was reduced after a second spinal transection at the Th12 level, while rhythms in the hindlimb remained unchanged. It thus appears that in the spinal preparation and under certain pharmacological conditions, phrenic bursts generated by the cervico-thoracic spinal cord can be driven by the lumbar generators of locomotion; spinal links thus exist between these hindlimb locomotion generators and spinal interneuronal networks involved in phrenic motoneuronal activation, may be via hindlimb forelimb driving.     

Evidence that C1 and C2 propriospinal neurons mediate the inhibitory effects of viscerosomatic spinal afferent input on primate spinothalamic tract neurons.

1. Lumbosacral spinothalamic tract (STT) neurons can be inhibited by noxious pinch of the contralateral hindlimb or either forelimb and by electrical stimulation of cardiopulmonary sympathetic, splanchnic, and hypogastric afferents. A previous study found that spinal transections between C2 and C4 sometimes abolished the inhibitory effect of spinal afferent input and sometimes left it intact. This suggested that propriospinal neurons in the C1 and C2 segments might mediate this effect. To test whether neurons in the C1 and C2 segments were involved in producing this inhibitory effect, the magnitude of the reduction in neural activity was measured in the same STT neuron before and after spinal transection at C1 or between C3 and C7. 2. All neurons were antidromically activated from the contralateral thalamus and thoracic spinal cord. For us to accept a neuron for analysis, the characteristics of the somatic input and the latency and shape of the antidromatic spike produced by spinal cord stimulation had to be the same before and after the spinal transection. Also, spinal transection often causes a marked increase in spontaneous cell activity, which may affect the magnitude of an inhibitory response. To avoid this confounding problem, a cell was accepted for analysis only if it showed marked inhibition of high cell activity evoked by somatic pinch before spinal transection. For analysis 13 STT neurons met these criteria: 6 neurons were in monkeys with C1 transections, and 7 neurons were in animals with transections between C3 and C7.(ABSTRACT TRUNCATED AT 250 WORDS)     

Different mechanisms involved in supraspinal and spinal reflex regulation of phrenic activity through chest movements

The coordination of breathing activity with chest movements was compared in the same decorticate rabbit preparations prior to and after a transection at the C2 spinal level. Pharmacological activation was induced with a combination of nialamide and DOPA in the latter situation. The preparation was curarized and chest inflations and deflations were induced by a respirator whose parameters could be modified. In decorticate preparations, phrenic activity was coordinated 1:1 with the respirator period over a large range of imposed periods. Beyond the extreme values a new coupling was achieved with a ratio of either 1:2 or 2:1. Throughout the range of 1:1 coordination, phrenic bursting always happened at a preferred time in the respirator period, although this time differed for the various imposed periods. This coordinated activity required vagal inputs. After spinal transection the phrenic nerves were totally silent; DOPA administration allowed rhythmic activity to develop. In some preparations, phrenic bursts were coordinated 1:1 with the respirator period and remained so for all the imposed periods: the phase of these phrenic discharges relative to the respirator cycle was kept unchanged for the different periods. In addition, there was a modulation of amplitude superimposed on this 1:1 coupling. These spinal phrenic bursts were generally suppressed when the respirator was turned off. From these results, the coordination of phrenic activity with the respirator rate appears to be produced by different mechanisms in the decorticate and in the spinal preparations. In the decorticate animal the periodic vagal inflow reset the activity of the medullary inspiratory generator and entrains it at its own rate. The coordination observed in the spinal preparation results from a periodic peripheral activation of premotoneuronal or motoneural phrenic elements during inflation. If the central bursts provided by the spinal "respiration" generator can fire phrenic motoneurons above threshold, their timing is not dependent on the peripheral inflow; when the motoneurons are fired below threshold by these central inputs, they are probably summing together the central and peripheral excitations, which could account for the amplitude modulation of the coordinated phrenic bursts of pure reflex origin. Possible afferent pathways are discussed.     

Anticonvulsant A(1) receptor-mediated adenosine action on neuronal networks in the brainstem-spinal cord of newborn rats

Membrane potential of ventral respiratory group neurons as well as inspiratory-related cranial (hypoglossal) and spinal (C(1)-Th(4)) nerve activities were analysed in brainstem-spinal cord preparations from neonatal rats. Block of Cl(-)-mediated inhibition with bicuculline (plus strychnine) affected neither rhythmic depolarizations nor spike discharge in 23 of 30 ventral respiratory group cells. In the other seven neurons, block of inhibitory postsynaptic potentials evoked pronounced depolarizations and spike discharge that was synchronous with seizure-like spinal nerve activity. Respiratory hypoglossal nerve activity persisted after transection at the spinomedullary junction, whereas spinal rhythm was blocked. After transection, the moderate bicuculline-evoked seizure-like perturbation of hypoglossal nerve activity was abolished and rhythmic ventral respiratory group neuron activity was not disturbed, whereas epileptiform discharge persisted in spinal nerves. The seizure-like nerve activity and depolarization of the minor subpopulation of perturbed ventral respiratory group neurons were reversed by either adenosine or the A(1) adenosine receptor agonist 2-chloro-N(6)-cyclopentyladenosine. The A(2) receptor agonist CGS 21860 had no effect. In control preparations, inspiratory nerve activity and membrane potential fluctuations (29 of 35 cells) were not changed by adenosine, 2-chloro-N(6)-cyclopentyladenosine or CGS 21860. In the other six cells, adenosine evoked a hyperpolarization (<10 mV) with no major change in input resistance. The anticonvulsant effects of adenosine and 2-chloro-N(6)-cyclopentyladenosine were antagonized by the A(1) adenosine receptor blocker 8-cyclopentyl-1,3-dipropylxanthine. After pre-incubation with 8-cyclopentyl-1,3-dipropylxanthine, bicuculline also evoked seizure-like discharge in the hypoglossal nerve.The results indicate that seizure-like spinal motor output of the respiratory network upon block of Cl(-)-mediated inhibition is caused by disinhibition of spinal neuronal networks with afferent connections to the ventral respiratory group. Presynaptic A(1) adenosine receptors exert an anticonvulsant action on the disinhibited spinal motor network, but have no depressing effect per se on the isolated medullary respiratory network.