Peroneal Motoneurons Research Articles

Misdirection of regenerating motor axons after nerve injury and repair in the rat sciatic nerve model

Misdirection of regenerating axons is one of the factors that can explain the poor results often found after nerve injury and repair. In this study, we quantified the degree of misdirection and the effect on recovery of function after different types of nerve injury and repair in the rat sciatic nerve model; crush injury, direct coaptation, and autograft repair. Sequential tracing with retrograde labeling of the peroneal nerve before and 8 weeks after nerve injury and repair was performed to quantify the accuracy of motor axon regeneration. Digital video analysis of ankle motion was used to investigate the recovery of function. In addition, serial compound action potential recordings and nerve and muscle morphometry were performed. In our study, accuracy of motor axon regeneration was found to be limited; only 71% (± 4.9%) of the peroneal motoneurons were correctly directed 2 months after sciatic crush injury, 42% (± 4.2%) after direct coaptation, and 25% (± 6.6%) after autograft repair. Recovery of ankle motion was incomplete after all types of nerve injury and repair and demonstrated a disturbed balance of ankle plantar and dorsiflexion. The number of motoneurons from which axons had regenerated was not significantly different from normal. The number of myelinated axons was significantly increased distal to the site of injury. Misdirection of regenerating motor axons is a major factor in the poor recovery of nerves that innervate different muscles. The results of this study can be used as basis for developing new nerve repair techniques that may improve the accuracy of regeneration.

Effects on peroneal motoneurons of cutaneous afferents activated by mechanical or electrical stimulations.

The postsynaptic potentials elicited in peroneal motoneurons by either mechanical stimulation of cutaneous areas innervated by the superficial peroneal nerve (SP) or repetitive electrical stimulation of SP were compared in anesthetized cats. After denervation of the foot sparing only the territory of SP terminal branches, reproducible mechanical stimulations were applied by pressure on the plantar surface of the toes via a plastic disk attached to a servo-length device, causing a mild compression of toes. This stimulus evoked small but consistent postsynaptic potentials in every peroneal motoneuron. Weak stimuli elicited only excitatory postsynaptic potentials (EPSPs), whereas increase in stimulation strength allowed distinction of three patterns of response. In about one half of the sample, mechanical stimulation or trains of 20/s electric pulses at strengths up to six times the threshold of the most excitable fibers in the nerve evoked only EPSPs. Responses to electrical stimulation appeared with 3-7 ms central latencies, suggesting oligosynaptic pathways. In another, smaller fraction of the sample, inhibitory postsynaptic potentials (IPSPs) appeared with an increase of stimulation strength, and the last fraction showed a mixed pattern of excitation and inhibition. In 24 of 32 motoneurons where electrical and mechanical effects could be compared, the responses were similar, and in 6 others, they changed from pure excitation on mechanical stimulation to mixed on electrical stimulation. With both kinds of stimulation, stronger stimulations were required to evoke inhibitory postsynaptic potentials (IPSPs), which appeared at longer central latencies than EPSPs, indicating longer interneuronal pathways. The similarity of responses to mechanical and electrical stimulation in a majority of peroneal motoneurons suggests that the effects of commonly used electrical stimulation are good predictors of the responses of peroneal motoneurons to natural skin stimulation. The different types of responses to cutaneous afferents from SP territory reflect a complex connectivity allowing modulations of cutaneous reflex responses in various postures and gaits.

Cooperation of muscle and cutaneous afferents in the feedback of contraction to peroneal motoneurons.

Peroneal motoneurons were recorded intracellularly in anesthetized cats during sustained submaximal contractions of peroneus brevis muscle (PB) elicited by repetitive electrical stimulation of motor axons in the distal portion of cut ventral root filaments. Mechanical stimulation of the territory innervated by the superficial peroneal nerve (SP) was applied during contraction to assess the influence of afferents from this territory on the contraction-induced excitation of motoneurons. In 21 peroneal motoneurons in which PB contraction evoked excitatory potentials, a stimulation engaging mechanoreceptors located in the skin around toes was found to either enhance (in 12 motoneurons) or reduce (in 9 motoneurons) the contraction-induced excitatory potentials. Among positive effects, six showed simple summation of the responses to each individual stimulus, suggesting a convergence of afferent pathways on motoneurons. In six other motoneurons, complex interactions were observed, as may result from convergence at a premotoneuronal level. Among negative effects, a single instance was observed of inhibitory facilitation, as may result from convergence of cutaneous and muscular, possibly Ib, afferents on inhibitory interneurons. Several pathways, mediating either facilitory or inhibitory influences, are available for cooperation of muscle and cutaneous input, allowing flexibility of motoneuron activation in different tasks.

Changes in expression of NMDA receptor subunits in the rat lumbar spinal cord following neonatal nerve injury.

The vulnerability of motoneurones to glutamate has been implicated in neurological disorders such as amyotrophic lateral sclerosis but it is not known whether specific receptor subtypes mediate this effect. In order to investigate this further, the expression of N-methyl-D-aspartate (NMDA) receptor subunits was studied during the first three post-natal weeks when motoneurones are differentially vulnerable to injury following neonatal nerve crush compared to the adult. Unilateral nerve crush was carried out at day 2 after birth (P2) which causes a decrease of 66% in motoneurone number by 14 days (P14). To study receptor expression in identified motoneurones, serial section analysis was carried out on retrogradely labelled common peroneal (CP) motoneurones by combined immunocytochemistry and in situ hybridization (ISH). mRNA levels were also quantified in homogenates from lumbar spinal cords in which the side ipsilateral to the crush was separated from the contralateral side. The NR1 subunit of the NMDA receptor was widely distributed in the spinal cord being expressed most strongly in motoneurone somata particularly during the neonatal period (P3-P7). The NR2 subunits were also expressed at higher levels in the somata and dendrites of neonatal motoneurones compared to older animals. NR2B mRNA was expressed at low to moderate levels throughout the studied period whereas NR2A mRNA levels were low until P21. Following unilateral nerve crush, an initial decrease in NR1 mRNA occurred at one day after nerve crush (P3) in labelled CP motoneurones ipsilateral to the crush which was followed by a significant increase in NR1 subunit expression at 5 days post-injury. This increase was bilateral although reaching greater significance ipsilateral to the crush compared with sham-operated animals. A significant increase in NR1 and NR2B mRNA post injury was also detected in spinal cord homogenates. In addition, the changes in levels of NR1 and NR2B mRNA were reflected by comparable bilateral changes at P7 in receptor protein determined by quantitative immunocytochemical analysis of NR1 and NR2 subunit expression in identified CP motoneurones indicating a co-ordinated regulation of receptor subunits in response to injury.

Short-latency synaptic patterns among cat peroneal motoneurons

Motoneurons innervating peroneal muscles in the cat leg (PB, PT and PL, respectively, for peroneus brevis, tertius and longus) were examined for their connections with afferents from these and other leg muscles and with cutaneous afferents. The aim was to investigate (1) whether inputs from nearby muscles and cutaneous areas are likely to assist or oppose the excitation elicited in peroneal motoneurons by PB contractions, and (2) whether reflex connectivity might allow distinction of α (i.e. motoneurons innervating skeletal muscle fibres) and β (i.e. motoneurons innervating both skeletal and intrafusal muscle fibres) subgroups among PB and PT motoneurons. In the three peroneal pools, every motoneuron had excitatory monosynaptic connections with Ia afferents from each of the three peroneal muscles, and nearly every motoneuron received di- or trisynaptic excitation from low-threshold cutaneous afferents in sural or superficial peroneal nerves. Inputs from these sources might facilitate the contraction-induced positive feedback. In contrast, the patterns of short-latency synaptic connections with group I afferents from pretibial flexor and post-tibial extensor muscles were heterogeneous among peroneal motoneurons but did not point to any specific β pattern.

Contraction-induced excitation in cat peroneal motoneurons.

1. Motoneurons innervating peroneal muscles were recorded intracellularly in anesthetized cats during sustained submaximal isometric contractions of peroneus brevis produced by repetitive electrical stimulation of motor axons in the distal portion of cut ventral root filaments. 2. In contrast with the inhibition previously observed during contractions of gastrocnemius medialis muscle in triceps surae motoneurons, the afferent input generated by peroneus brevis contraction elicited excitatory potentials in nearly all motoneurons supplying peroneus brevis, peroneus tertius, or peroneus longus muscles. 3. We ascribed the contraction-induced excitation of peroneal motoneurons to spindle afferents for two reasons. First, the amplitude of contraction-induced excitatory potentials increased when the ventral root stimulation strength was increased to recruit gamma-axons. Second, with stimulation strengths under gamma-threshold, peroneus brevis contraction still excited peroneal motoneurons, and we obtained evidence that activation of spindles by skeletofusimotor beta-axons could account at least partly for this excitation. 4. The lack of contraction-induced inhibition in peroneal motoneurons and the prevalence of contraction-induced excitation raised the possibility that, in contrast to the usual effects of tendon organ afferents, Ib afferents from peroneus brevis might exert an excitatory influence on homonymous motoneurons. The fact that electrical stimulation of group I afferents in the nerve to peroneus brevis only exceptionally evoked inhibition in peroneal motoneurons would appear compatible with this hypothesis. Furthermore, stimulation of cutaneous afferents, known to facilitate transmission in Ib pathways, only exceptionally revealed a weak contraction-induced inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

All peroneal motoneurons of the rat survive crush injury but some fail to reinnervate their original targets

This is a quantitative study of the motoneuronal population of the rat's common peroneal nerve following severe crush injury of the sciatic nerve or its component branches. The crush was performed unilaterally under anesthesia for 60 seconds with hemostat jaws covered with tubing to form a smooth, 2 mm long, injured zone. Recovery from injury was allowed for 14 to 188 days. It was measured behaviorally using the sciatic functional index (SFI) and electrophysiologically by comparing the conduction velocity and amplitudes of evoked muscle action potentials prior to injury, and again after injury just before the nerve was labeled with horseradish peroxidase (HRP), and/or its wheat germ agglutinin conjugate (WGA-HRP), 48-72 hours before sacrifice. The motoneurons were retrogradely labeled on both sides so that the uninjured side might serve as a control. On the injured side the nerves were labeled either distal or proximal to the crush site. The tibialis anterior muscles on both sides were removed and weighted. Spinal segments L2 to L6 were cut in serial, frozen cross-sections. HRP reaction products were formed using TMB as the chromogen. The normal peroneal nerve was found to contain 634 +/- 26 motoneurons (22 cases). The number of motoneurons labeled 5-15 mm distal to the injury site (22 cases) was 535 +/- 69 or 84.4% of normal. In 12 cases in which the nerve was labeled 5 mm proximal to the injury normal population numbers (648 +/- 30) were found. These counts demonstrated that the unlabeled 15.6% in the distal labeled cases had not vanished as a result of cell death. Instead, the unlabeled group was composed mainly of small motoneurons whose axons probably had not regenerated distal to the crushed zone. Mean soma size of injured neurons increased to maximum 3-6 weeks after injury and then gradually decreased in size over the following weeks to nearly normal values. This transient increase in size was due to two factors: 1) soma swelling in response to axonal injury, and 2) absence of many small motoneurons, presumably gamma-motoneurons, which were either incapable of, or prevented from, regenerating beyond the injury zone long after larger motoneurons had reinnervated their targets. SFI scores, muscle weights, and amplitude ratios of evoked potentials recovered to control values by 70-80 days post-injury. Conduction velocities remained 20-25% below normal at the end of 80 days.(ABSTRACT TRUNCATED AT 400 WORDS)

Postnatal development of peroneal motoneurons in the kitten

In 1- to 72-day-old kittens, motoneurons of the 3 peroneal muscle nuclei were labeled by retrograde axonal transport of horseradish peroxidase from individual muscles. At birth, the locations of peroneal nuclei were similar to those of the adult cat. Counts of motoneurons at different ages indicated that postnatal cell death does not occur in peroneal motor nuclei. Primary dendrites were as numerous in motoneurons of newborn kittens as in adult motoneurons but they were thinner, shorter and poorly ramified. The number of recurrent axon collaterals was higher in the first postnatal week than at later stages. The growth of motoneurons followed similar rates in the 3 peroneal nuclei. Distributions of cell body diameters and volumes were unimodal at birth and became bimodal between 15 and 20 days postnatal. The separation of peroneal motoneurons in two size subgroups, presumably corresponding to α and γ populations, was followed by an increase in growth rate which became faster for α than for γ motoneurons.

Soma size and oxidative enzyme activity in normal and chronically stimulated motoneurones of the Cat's spinal cord

In normal adult cats we measured the density of staining for the activity of succinate dehydrogenase (SDH staining) in ventral horn cells of different sizes. The measurements were restricted to that part of the lumbar ventral horn (L6–L7) which is known to contain motoneurones of the peroneal nerve. A statistically significant tendency was found for the SDH staining to be denser in smaller than in larger neurones within the size range of α motoneurones (soma diameter40 μm). These results are consistent with recently published evidence for ventral horn cells of rats and qualitatively similar relationships between size and SDH staining have also been observed among skeletal muscle fibres (confirmed for mixed muscle of cat in present study). In hindlimb muscles, size as well as SDH staining are known to be markedly activity-dependent. We tested whether this is the case for peroneal motoneurones as well by analyzing the effects of chronic nerve stimulation on the properties of neurones within the appropriate region of the ventral horn. Prior to the final acute experiment, these cats had been subjected to a left-side dorsal rhizotomy and hemispinalization. By aid of a portable mini-stimulator, the left-side common peroneal nerve was activated by repetitive pulses during 50% of total time per day (intra-activity rate: 10, 20 or 40 Hz). After 8 weeks of such treatment, cell sizes as well as the densities of SDH staining showed hardly any differences between peroneal ventral horn cells of the experimental and control sides of the spinal cord. Thus, with respect to the analyzed cell properties, motoneurones seem to be markedly less activity-dependent than is known to be the case for their muscle fibres.

Motor-unit organization in flexor digitorum longus muscle of the cat.

Motor-unit organization in flexor digitorum longus muscle of the cat.R P Dum, R E Burke, M J O'Donovan, J Toop, and J A HodgsonR P Dum, R E Burke, M J O'Donovan, J Toop, and J A HodgsonPublished Online:01 Jun 1982https://doi.org/10.1152/jn.1982.47.6.1108MoreSectionsPDF (3 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByTonic and Phasic Discharge Patterns in Toe Flexor γ-Motoneurons During Locomotion in the Decerebrate CatP. R. Murphy1 January 2002 | Journal of Neurophysiology, Vol. 87, No. 1Force-Frequency and Fatigue Properties of Motor Units in Muscles That Control Digits of the Human HandAndrew J. Fuglevand, Vaughan G. Macefield, and Brenda Bigland-Ritchie1 April 1999 | Journal of Neurophysiology, Vol. 81, No. 4Organization of Recurrent Inhibition and Facilitation in Motor Nuclei Innervating Ankle Muscles of the CatVladimir V. Turkin, Katrina S. Monroe, and Thomas M. Hamm1 February 1998 | Journal of Neurophysiology, Vol. 79, No. 2Anatomical and physiological study of interneurons in an oligosynaptic cutaneous reflex pathway in the cat hindlimbBrain Research, Vol. 586, No. 2Postnatal development of peroneal motoneurons in the kittenDevelopmental Brain Research, Vol. 54, No. 2Neuronal and muscle unit properties at different rostro-caudal levels of cat's motoneurone poolBrain Research, Vol. 335, No. 1Somatotopic relations between the motor nucleus and its innervated muscle fibers in the cat tibialis anteriorExperimental Neurology, Vol. 86, No. 2Relation between location of a motor unit in the human biceps brachii and its critical firing levels for different tasksExperimental Neurology, Vol. 85, No. 3The development of the spinal motor column in relation to the myotomal muscle fibers in the zebrafish (Brachydanio rerio)Anatomy and Embryology, Vol. 167, No. 1 More from this issue > Volume 47Issue 6June 1982Pages 1108-25 https://doi.org/10.1152/jn.1982.47.6.1108PubMed7108574History Published online 1 June 1982 Published in print 1 June 1982 Metrics

Anatomy of medial gastrocnemius and soleus motor nuclei in cat spinal cord.

Anatomy of medial gastrocnemius and soleus motor nuclei in cat spinal cord.

Motor cell columns in rat lumbar spinal cord.

The distribution pattern of motoneurons in the rat's lumbar spinal cord which send axons to the sciatic nerve was studied by means of staining degenerated motor cells with toluidine blue after relevant roots or nerves had been sectioned or crushed. The columnar arrangement of the motor cells in the lumbar spinal cord of the normal rats was confirmed and presented. The degeneration picture of the rat motoneuron was presented, which was observed only in the large cells in the ventral horn and not in the smaller cells suggestive of γ-motoneurons. It was found that the sciatic motoneurons occupy the dorsolateral portion of the ventral horn and extend in proximocaudal direction from the mid L4 through L5 to the end of L6. It was proved that the tibial motoneurons innervating the extensors of lower hind-limb and foot are situated dorsolaterally in the sciatic portion of the columnar arrangement of the motor cells, while the peroneal motoneurons innervating the flexors of lower hind-limb occupy the medial section in the sciatic portion.

Electrophysiological study of consecutive changes of feline ventral root reflexes during degeneration and regeneration following peripheral nerve section

Electrophysiological data which record the consecutive changes of monosynaptic and polysynaptic ventral (L7) root reflexes during retrograde degeneration and axon regeneration are presented. In cats the left posterior tibial nerve was subjected to a 1-cm resection. In one series of animals the surgical procedure included tubulation of the nerve stumps with a Millipore tube for repair; in the second series of animals nerve regeneration was prevented. Significant changes, characterized by monosynaptic failure and enormous preponderance of the polysynaptic reflex component on the operated side, dominated the reflex picture during the stages of muscle denervation. As soon as neuromuscular connections for afferent and efferent alpha fibers could be demonstrated (at 6 weeks after surgery), gradual restitution of the abnormal motoneuron reflex activity commenced. Return of normal motoneuron reflex function was seen between the twelfth and sixteenth postoperative weeks. Transient similar changes of the reflex activity in ipsilateral segmental peroneal (antagonistic) motoneurons, not directly affected by the procedure of posterior tibial nerve section, was commonly seen during the period of the gastrocnemius and scleus muscle denervation. Ventral root reflexes elicited from the regenerating nerve stump distal to the original lesion revealed abnormalities of the myotatic reflex action which lasted long after refunctioning large fiber components of the nerve could be demonstrated. The proprioceptive spike component on the operated side was never equally restituted to that obtained on the control side in terms of virtual synchrony and amplitude, even in experiments continuing up to 58 weeks after surgery. The demonstrated dysfunction of ventral root reflexes during the period of neuromuscular regeneration leading to a deficiency in the myotatic reflex action is discussed as one among other factors, which temporarily is likely to interfere with proper muscle function long after axonal continuity between nerve and muscle has been established.

Intracellular Study of Recurrent Facilitation

Recurrent facilitation in the cat's spinal cord has been studied in deep peroneal and quadriceps motoneurons with the use of intracellular recording. The presence of facilitation was indicated by several criteria, among them increased firing index of the cells or decreased latency of firing. In many, but not all, facilitated cells the conditioning volley caused a small visible depolarization. Subthreshold synaptic potentials were frequently increased in magnitude by the conditioning volley, which also increased the effectiveness of a stimulus applied through the microelectrode. Facilitation was found in a large percentage of the motoneurons investigated and was clearly able to bring about pronounced changes in the excitability and firing behavior of these cells.