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R H Westgaard

Publications and source records attributed to R H Westgaard.

At least 73 records · Page 4Linked to original sources
PubMed1984

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.

Action Potentials↗
PubMed1982

Variations in the time course of the synchronization of intercostal motoneurones in the cat.

1. Synchronization of intercostal motoneurones was studied by the construction of cross-correlation histograms which related the firing times of paired groups of efferent inspiratory or expiratory discharges recorded from filaments of the external or internal nerves of anaesthetized or decerebrate cats.2. The principal feature of the histograms was always a central peak but the time course of the central peak showed considerable variation. Three forms of synchronization were defined on the basis of the time course of the central peak: (i) short-term synchronization (Sears & Stagg, 1976), where the peak was narrow, extending over about +/-3 ms but sometimes with weak shoulders to about +/-5 ms; (ii) broad-peak synchronization where the peak was wider than this (often +/-20 ms or more) but where there were no strong periodicities; (iii) high-frequency oscillation (h.f.o) synchronization, which was named from the related phenomena in medullary and phrenic recordings (Cohen, 1979), where there were periodic peaks on either side of the central peak with a frequency in the range 60-120 Hz. Combinations of these forms of synchronization were seen in some histograms.3. When different animals were compared, broad peak synchronization was seen in association with light anaesthesia and with polysynaptic excitation of the motoneurones from muscle spindle afferents.4. In individual animals, additional anaesthesia depressed both broad peak and h.f.o. synchronization.5. Raising P(A, CO2), which increased the respiratory drive to the motoneurones, favoured short-term or h.f.o. synchronization at the expense of broad-peak synchronization.6. In three decerebrate animals only short-term or h.f.o. synchronization was seen.7. Spinal cord lesions above or below the segments of interest promoted broad-peak synchronization, even with high P(A, CO2) or deep anaesthesia.8. We conclude: (i) that short-term synchronization, due mainly to the branching of presynaptic axons, is generated mainly by those axons which transmit the respiratory drive, that drive providing most of the excitation of the motoneurones in moderately deep anaesthesia; (ii) that h.f.o. synchronization arises from the periodic synchronization of the discharges in these same presynaptic axons; (iii) that broad-peak synchronization is generated by the activity of other presynaptic neurones whose discharges are also synchronized, but aperiodically, these neurones most likely including spinal cord interneurones which are active in light anaesthesia or when released by spinal cord lesions.9. These conclusions are supported by comparisons between intracellular recordings from inspiratory motoneurones in animals showing different forms of motoneurone synchronization, the comparison including the measurements of ;average common excitation' (a.c.e.) potentials (Kirkwood & Sears, 1978).

Action Potentials↗
PubMed1982

The spatial distribution of synchronization of intercostal motoneurones in the cat.

1. The three different types of synchronization of intercostal motoneurones which were described in the preceding paper (Kirkwood, Sears, Tuck & Westgaard, 1982) were studied for motoneurones of the same segment or for different segmental separations (up to five segments) and for motoneurones on opposite sides of the same segment.2. The strength of synchronization declined with segmental separation for all three categories, although the rate of decline was more variable for broad-peak synchronization than for the two other types. Short-term synchronization was undetectable for separations greater than three or four segments but clear peaks were still visible in the cross correlation histograms for high-frequency oscillation (h.f.o.) or broad-peak synchronization at a segmental separation of five. Synchronization between motoneurones on opposite sides of the cord was generally weak although less so for broad-peak or h.f.o. components.3. The decline in strength of short-term synchronization with segmental separation could not be explained by temporal dispersion of impulses in presynaptic axons.4. A time shift was observed in the position of the cross-correlation histogram peak which was dependent on segmental separation and equivalent to a mean descending conduction velocity of 28 m/s in the assumed common input. This figure is similar to the mean conduction velocity of bulbospinal respiratory neurones derived from published values.5. We conclude that the short-term synchronization in these preparations is generated by the bulbospinal respiratory neurones and that the majority of their axons do not branch to make strong synaptic connexions to motoneurones over more than three to four segments.6. Interpretations of the different distributions of the other types of synchronization are discussed.

Action Potentials↗
PubMed1981

Recurrent inhibition of intercostal motoneurones in the cat.

1. The external and internal intercostal nerves of a single intercostal space were stimulated in anaesthetized paralysed cats with dorsal roots cut in the corresponding spinal cord segment. 2. Extracellular recording in the ventral horn revealed single units which fired short high frequency bursts of spikes at short latency to stimulation of either or both of the two nerves at stimulus strengths appropriate to the activation of alpha motor axons. These units were deduced to be Renshaw cells. 3. Small (0.1-0.2 mV) hyperpolarizing potentials of duration up to 50 msec were recorded intracellularly in both inspiratory and expiratory motoneurones of the same segment. Latencies and thresholds were appropriate for disynaptic i.p.s.p.s evoked by collaterals of alpha motor axons. 4. The changes in probability of firing following the stimuli were examined for inspiratory alpha motoneurones by constructing post-stimulus histograms of efferent discharges recorded from filaments of the external intercostal nerve of the segment stimulated and from other segments. 5. A period of reduced probability of firing of up to 24 msec duration, corresponding in all respects to disynaptic inhibition from alpha motor axon collaterals, was seen in the segment stimulated and up to three segments distant, though declining in intensity with distance. Either nerve could evoke such inhibition although that evoked from the internal intercostal nerve was stronger, as were the intensities of the Renshaw cell discharges. 6. We conclude that recurrent inhibition, via Renshaw cells which have axons up to 30 mm in length, is present for intercostal motoneurones. Arguments are adduced to show that although the effects from stimulating any one segmental nerve may be relatively weak, the over-all effect resulting from the widely spread projections of the Renshaw cells concerned is an inhibition comparable intensity with that seen in many hind limb motor nuclei.

Action Potentials↗
PubMed1980

The morphology of rat soleus neuromuscular junctions treated in vitro with purified beta-bungarotoxin.

Pairs of isolated rat soleus nerve-muscle preparations were maintained in vitro in oxygenated Ringer solution containing 3 microgram/ml beta-bungarotoxin prepared by the method of MacDermot et al. End-plate potentials and twitch tensions generated in response to continuous stimulation via the nerve at 0.5 Hz were recorded from one muscle, while miniature end-plate potential amplitude and frequencies were monitored in the corresponding unstimulated member of the pair. The results obtained were compared with the fine structure of end-plates from identical preparations sampled after varying periods of intoxication, and from unpoisoned muscles maintained for comparable times in vitro. The electron micrographs obtained were analyzed quantitatively using simple stereological techniques. Our results show that: (1) nerve terminal synaptic vesicle content declines for the first hour of intoxication but returns to near normal levels following conduction block; (2) there is a rapid increase in the 'coated' vesicle population of the nerve terminals, both attached to the plasmalemma and within the terminal cytoplasm, which persists to the end of the experiment; and that (3) there is no significant increase in the incidence of damaged mitochondria within the poisoned nerve terminals. These findings are discussed in relation to previous observations and the putative mechanisms of action of beta-bungarotoxin.

Animals↗
PubMed1978

beta-Bungarotoxin. Separation of two discrete proteins with different synaptic actions.

beta-Bungarotoxin, a specific presynaptic blocking agent, was prepared in two stages from the crude venom of Bungarus multicinctus by ion-exchange chromatography on the weakly acidic ion exchanger, CM-Sephadex, and on the strongly acidic ion exchanger, sulphopropyl-Sephadex. By these procedures it was purified to a single protein, which was shown by reduction to contain two polypeptide chains with mol.wts. of less than 15000. During purification of beta-bungarotoxin three other proteins were isolated. Two of these proteins have similar molecular weights, subunit structure and physiological properties to the major protein component. This latter is referred to as beta-bungarotoxin, since it has the same physiological properties as those described for unpurified beta-bungarotoxin by other workers. The first protein has very different physiological effects and biochemical properties from beta-bungarotoxin. This protein has a single class of polypeptide chains with an apparent molecular weight that is lower than the main beta-bungarotoxin protein, and appears to block synaptic transmission by a predominantly postsynaptic effect. It has been suggested [Oberg & Kelly (1976) J. Neurobiol. 7, 129-141] that the action of beta-bungarotoxin depends on its phospholipase A activity; however, in this preparation of the toxin less than 50 muunits of phospholipase A activity were detected (1 unit of activity is the amount of enzyme forming 1 mumol of L-alpha-phosphatidylcholine/min per mg of protein).

Animals↗
PubMed1978

beta-Bungarotoxin. The binding of [3H]pyridoxylated beta-bungarotoxin to a high-molecular-weight protein receptor.

beta-Bungarotoxin was labelled with pyridoxal 5'-phosphate (incorporating 3H). The kinetics of beta-bungarotoxin binding to several tissue subfragments of nervous tissue was studied. The dissociation constant of 3H-pyridoxylated beta-bungarotoxin in this reaction was 0.21-0.37 micron and that of unlabelled beta-bungarotoxin was 25 nM. Hill [(1910) J. Physiol. (London) 40, iv-vii] and Scatchard [(1949) Ann. N.Y. Acad. Sci. 51, 660-672] analyses demonstrated no co-operativity of binding and only a single class of receptor sites, consistent with a bimolecular association of beta-bungarotoxin and its receptor. The iodinated toxin was physiologically inactive. Toxin was bound in non-specific unsaturable fashion by glass and/or plastic. This low-affinity binding was corrected by addition of bovine serum albumin to a final concentration of 30 mg/ml. A soluble protein receptor of beta-bungarotoxin was isolated and the mol.wt. is approx. 200000.

Animals↗
PubMed1978

Extrajunctional acetylcholine sensitivity of inactive muscle fibres in the baboon during prolonged nerve pressure block.

1. Nerve-evoked muscular activity was abolished in the small hand muscles of the baboon for 1-2 months by a 3 hr period of nerve compression from a pneumatic tourniquet inflated round the forearm. In the large diameter nerve fibres, this produced either a prolonged conduction block due to local myelin damage at the site of compression, or (in 10-30% of the large fibres) Wallerian degeneration. 2. At varying intervals after nerve compression the extrajunctional acetylcholine (ACh)-sensitivity of innervated but inactive muscle fibres in the fourth lumbrical muscle was measured. Observations were also made on lumbrical muscle fibres at similar intervals after surgical denervation. 3. The ACh sensitivity of nerve-blocked muscle fibres started to develop later than in denervated muscle fibres (10 vs. 7 days) and remained at a lower level (40-80 mV/nC, median ACh-sensitivity) than that of denervated muscle fibres (200-437 mV/nC) from 21 to 63 days after nerve block or denervation. 4. In stimulation experiments on four muscles, extrajunctional ACh-sensitivity of both denervated and innervated but inactive fourth lumbrical muscle fibres was reduced by muscular activity. 5. In four animals mild compression was used in the lower limb to produce persistent nerve block without Wallerian degeneration. With one exception (in which some Wallerian degeneration had occurred) recording with a co-axial needle from abductor hallucis showed no spontaneous fibrillation up to 28 days after compression, although the extrajunctional ACh-sensitivity of the muscle fibres appeared to reach levels similar to those observed in the forelimb. All four muscles developed a slight increase in insertion activity after 1-2 weeks. 6. It may be concluded that both muscular activity and some other neural influence, independent of muscular activity, are able to influence extrajunctional muscle properties in the baboon. The neural influence appears to be more effective in preventing spontaneous fibrillation than in preventing a rise in ACh sensitivity of the extrajunctional muscle membrane.

Acetylcholine↗
PubMed1975

The interaction between foreign and original motor nerves innervating the soleus muscle of rats.

1. The fibular nerve was transplanted on to the soleus muscle of the rats. Interruption of the original soleus nerve then permitted cross-innervation, and subsequently, over a period of weeks, re-innervation by the original nerve. 2. Individual muscle fibres were often innervated by both the original and the foreign nerve. The original and foreign end-plates were located in separate regions of the muscle. There were no indications that the original nerve could displace or repress the foreign innervation. 3. The extent of re-innervation by the original nerve depended upon the method of denervation. A single crush of the nerve was followed by virtually complete re-innervation, even of muscle fibres already innervated by the foreign nerve. When re-innervation was delayed by resection of a segment of the nerve only muscle fibres without foreign nerve innervation were re-innervated. Denervation by a simple nerve cut gave an intermediate result. 4. Re-innervation by the original nerve can take place without measurable extrajunctional sensitivity to ACh. 5. The original end-plate region could retain high and localized sensitivity to ACh for several months despite degeneration of its motor nerve terminal and activity of the muscle fibre. 6. Established foreign end-plates were re-innervated by the foreign nerve on muscle fibres with intact original innervation. 7. The factors controlling synapse formation in skeletal muscles are discussed.

Acetylcholine↗
PubMed1975

Influence of activity on the passive electrical properties of denervated soleus muscle fibres in the rat.

The technique of direct electrical stimulation of denervated muscle was used to study the role of muscle activity per se in controlling the passive electrical properties of muscle fibres. 2. Specific membrane resistance and capacitance of the denervated and the denervated-stimulated muscle fibres were measured by a sinewave technique at frequencies between 5 and 240 Hz. The parameter values were constant at low frequencies up to a variable transition frequency and declined rapidly at higher frequencies. 3. Following denervation the low-frequency value of specific membrane resistance increased (2291 omega cm2 for 19-day denervated fibres vs. 766 omega cm2 for innervated fibres), the specific membrane capacitance declined (2-7 muF/cm2 vs. 3-6 muF/cm2) and the transition frequency shifted towards lower frequencies. The specific internal resistance was higher in denervated fibres (301 omega cm for 19-day denervated fibres vs. 240 omega cm in innervated fibres) apart from a transient decline after 5 days of denervation (164 omega cm). 4. Direct electrical stimulation for 2 weeks beginning on the 5th day after denervation restored all parameters listed above to their original values before denervation. 5. Stimulation arrested in most cases further atrophy from the time of stimulation but did not restore normal fibre size.

Animals↗
PubMed1975

Further studies on the control of ACh sensitivity by muscle activity in the rat.

1. Denervated rat soleus muscles were stimulated directly through chronically implanted electrodes and the influence of different amounts and patterns of stimuli on the acetylcholine (ACh) sensitivity of the muscle was studied. The number of stimuli was varied by giving similar trains of stimuli (10 Hz for 10 sec) at different intervals (0 to 12 hr). The pattern of stimulation was varied by giving different trains of stimuli (100 Hz for 1 sec, 10 Hz for 10 sec and 1 Hz continuously) as the same average frequency of stimulation (1 Hz). 2. Stimulation usually started 5 days after the denervation when ACh hypersensitivity was fully developed. Most stimulation procedures reduced extrajunctional ACh sensitivity to normal or below normal values within 5-21 days, and these levels were maintained on prolonged stimulation. 3. The rate at which ACh hypersensitivity disappeared increased with increasing amount and frequency of stimulation. However, as few as 100 stimuli given every 5-5 hr for 3 weeks caused a tenfold reduction of sensitivity. 4. The stimulation had little or no effect on the ACh sensitivity at the end plate. Along the rest of the fibre the sensitivity was reduced at approximately the same rate except near the tendons where it appeared to fall more slowly in some fibres. 5. The stimulation restored the resting membrane potential of the denervated fibres to normal.

Acetylcholine↗
PubMed1973

Hyperinnervation of skeletal muscle fibers: dependence on muscle activity.

After the motor nerve to the rat soleus muscle was blocked reversibly by local anesthesia, individual muscle fibers became innervated by a transplanted motor nerve without losing their original innervation. Such cross-innervation of the denervated soleus muscle by the same foreign nerve was largely reduced by direct electrical stimulation of the muscle. The results demonstrate the importance of muscle activity for synapse formation by a foreign motor nerve.

Animals↗