Similar age-related changes in two regions of muscle with different properties.

Two regions of the medial gastrocnemius (MG) muscle, with different contractile properties and innervated by different nerve branches, were investigated in male Sprague-Dawley rats at three ages: 2-3 months, 6-7 months and 24-25 months (i.e., the '50% survival age and beyond': a recommended definition of aged rodents derived from lifespan data on a given colony). At the 50% survival age, both regions of the MG showed decreased mass, slowed contraction times and a decreased number of fast-twitch, but not slow-twitch, muscle fibres. The 40% loss of fast-twitch muscle fibres was not reflected in the loss of motoneurones, suggesting that muscle degeneration precedes motoneurone loss at the 50% survival age in the rat.

Motoneurons innervating two regions of rat medial gastrocnemius muscle with differing contractile and histochemical properties.

The medial gastrocnemius (MG) muscle, which receives its innervation by two extramuscular nerve branches, is representative of muscles which show a particular form of muscle compartmentalization (i.e. a regional specialization of muscle fibers) in which there is a 'deep' oxidative region and a 'superficial' low-oxidative region. Differential recruitment of motor units from these two regions of the MG has been reported for different functional tasks. Our goal was to determine if the organization of the MG motoneuron pool-muscle complex with its two extramuscular nerve branches could account for the phenomenon of regional specialization of muscle fibers. The two extramuscular nerve branches innervated muscle subvolumes which differed in contractile properties and fiber type percentages. The MG proximal nerve branch (NBr) innervated mostly high-oxidative and slow fibers, but with some low-oxidative fast fibers. The distal NBr innervated mostly low-oxidative fibers, but also a small proportion of high-oxidative and slow fibers. These results suggest that the two nerve branches do not strictly define a superficial/deep organization of fiber types in the MG. The number and soma size characteristics of motoneurons supplying the two extramuscular nerve branches showed that the motoneurons innervating the deep more oxidative muscle region, supplied by the proximal NBr, were smaller than those innervating the superficial, primarily low-oxidative, region supplied by the distal NBr. Our findings indicate that the MG motoneuron pool-muscle complex of the Sprague-Dawley rat will lend itself to studies of how the various motor unit types within a given spinal motor complex adapt to different conditions (e.g. aging, disease, injury, exercise).

Adult spinal motoneurons remain viable despite prolonged absence of functional synaptic contact with muscle.

Several rat medial gastrocnemius (MG) motor axons were allowed to regenerate into normally innervated muscle. Under these conditions, synapse formation is known to be prevented by the existence of the original innervation of the host muscle. A study was made of the ability of the implanted spinal motoneurons to acquire and retrogradely transport horseradish peroxidase (HRP) injected into the host muscle at various postoperative intervals. HRP-labeled MG motoneurons on the implanted side were observed at postoperative intervals as long as 290 days. A comparison of the number of labeled MG motoneurons on the implanted side versus the number on the unoperated, control side indicated no significant differences. At all investigated postoperative intervals except the earliest (7 DPO), a significant decrease in the mean MG motoneuron soma cross-sectional area was observed relative to the unoperated, control side. Analysis of labeled motoneuron size distributions showed that postoperative atrophy of larger, presumably alpha, motoneurons occurred at a significantly faster rate than in smaller, presumably gamma, motoneurons. These results demonstrate that axotomized adult spinal motoneurons survive and remain viable for prolonged periods when denied the opportunity to reinnervate muscle but do so in an atrophied state. The results indicate further that alpha and gamma motoneurons differ quantitatively in their responses to peripheral axotomy.

Incoordination in patients with hemiparesis.

Incoordination is frequently observed in patients following a cerebrovascular accident. Clinical electromyographic studies which have furthered our understanding of this motor impairment are reviewed, and possible underlying mechanisms are discussed. It is suggested that the lack of coordinated voluntary movement observed in hemiparetic patients may be due, in part, to an impaired regulation of spinal neurones. In the rehabilitation sciences, the need to assess the effectiveness of treatment as well as develop new approaches for the treatment of hemiparetic subjects will require the combined efforts of many investigators. A two-fold research approach is supported which aims: 1) to quantify the motor deficit, and 2) to extend our knowledge of the physiological mechanisms underlying the deficit. Such a general research approach could be of value to the study of other sensorimotor deficits.

Axotomy-like changes in cat motoneuron electrical properties elicited by botulinum toxin depend on the complete elimination of neuromuscular transmission.

The electrical properties of cat medial gastrocnemius (MG) spinal motoneurons were studied 14-21 d following injection of type A botulinum toxin (BTX) into the MG muscle. Treated MG muscles were atrophic, displayed pronounced fibrillation activity, and were markedly but not completely paralyzed. MG motoneuron electrical properties from animals with the highest MG muscle-twitch forces (greater than 20 gm) appeared normal, while motoneuron properties from animals with the lowest MG muscle-twitch forces (less than 10 gm) exhibited axotomy-like changes, though these changes were less pronounced than after axotomy itself. No changes in the axonal conduction velocity were observed, however. Motoneuron connectivity with MG muscle fibers was determined following intracellular stimulation of MG motoneurons by averaging EMG signals from 3 or 4 pairs of recording electrodes inserted into the BTX-treated MG muscles. Normal electrical properties were observed among motoneurons in which detectable EMG activity linked to the intracellular stimulation pulse was observed. The level of this connectivity, however, indicated that a relatively small number of muscle fibers were activated by individual motoneuron action potentials. Axotomy-like changes of electrical properties were observed in MG motoneurons that could not be associated with detectable EMG activity in the BTX-treated MG muscle following repeated trials of intracellular stimulation. These results indicate that the existence of effective neuromuscular transmission at a small number of motor terminals is sufficient to prevent the appearance of axotomy-like changes in motoneuron electrical properties, and that the absence of such transmission at all motor terminals is associated with the appearance of axotomy-like changes. The results suggest that the effects of axotomy itself on motoneuron properties may be based upon the loss or elimination of a potent interaction between muscle and motoneurons normally mediated by neuromuscular transmission.

Effects of preventing reinnervation on axotomized spinal motoneurons in the cat. I. Motoneuron electrical properties.

1. The intent of this study was to determine the effect on the electrical properties of axotomized spinal motoneurons when motor axons are allowed to regenerate but are denied the opportunity to reinnervate muscle. 2. The nerve supplying the medial gastrocnemius (MG) muscle in cats was served close to its entry into the muscle and sutured onto the surface of the lateral gastrocnemius (LG) muscle. The MG muscle was excised to prevent availability of vacant end-plates to the regenerating MG axons. The electrical properties of antidromically identified MG motoneurons were studied using intracellular recording at various postoperative intervals. 3. In 9 of 12 experimental animals, no sign of functional innervation by MG axons of the LG muscle could be detected. In three experimental animals, electrical and contraction activity in the LG muscle was observed following electrical stimulation of the transplanted MG nerve. The observed electrical and contraction activity was, however, negligible compared to the effects of electrical stimulation of the intact LG-soleus nerve. 4. At the earliest postoperative interval studied (20 days), MG motoneuron electrical properties [input resistance, afterhyperpolarization (AHP) duration, conduction velocity, time constant, rheobase current, and sag] exhibited significant changes that were nearly identical to those described for spinal motoneurons following section of ventral roots or motor nerves or in the earliest stages of reinnervation. 5. At the 44-60 day postoperative (DPO) intervals, several motoneuron electrical properties showed signs of recovery to control levels. At 44 DPO, average values of input resistance, time constant, and AHP duration declined from the significant increases observed at 20 DPO and could not be distinguished statistically from control mean values. 6. These indications of an early recovery of normal electrical properties were not sustained. At subsequent postoperative intervals (90, 120, and 150-180 DPO), average values of motoneuron electrical properties tended to be similar to those observed at 20 DPO. 7. Correlations observed among control motoneuron electrical properties were weakened and the pattern of correlation was disrupted at all postoperative intervals. 8. In conjunction with previous results demonstrating recovery of normal electrical properties following reinnervation (Foehring et al. 1986b), our findings suggest that functional contact with muscle is required for the full expression of the normal range of motoneuron electrical properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of preventing reinnervation on axotomized spinal motoneurons in the cat. II. Changes in group Ia synaptic function.

1. Composite excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of heteronymous group Ia afferents have been studied at various postoperative times in axotomized motoneurons that were denied the opportunity to reinnervate muscle. 2. The medial gastrocnemius (MG) nerve was transected and sutured onto the surface of the normally innervated lateral gastrocnemius (LG) muscle. The denervated MG muscle was excised thereby eliminating access of regenerating MG motor axons to vacant end-plates. 3. The mean amplitude of monosynaptic Ia EPSPs evoked by electrical stimulation of the LG-soleus (LGS) nerve and recorded in axotomized MG motoneurons showed an initial decline at 20 days postoperative (DPO) that was not significant. At 44 DPO, mean amplitude had declined significantly to 43% of the control mean amplitude. At 90 DPO, mean EPSP amplitude was not significantly different from control. At the latest postoperative time (150-180 DPO), mean amplitude was significantly less than the control amplitude. 4. Mean EPSP rise time (time-to-peak) was significantly increased (27%) at the earliest postoperative times (20-44 DPO). At later postoperative times (90-180), mean EPSP rise time was not significantly different from mean control rise time. 5. "Partial responses" superimposed on EPSPs were not observed at any postoperative time. 6. Mean posttetanic potentiation (PTP) of the LGS EPSP was significantly depressed at 20 DPO. At later postoperative times, PTP did not differ significantly from mean control PTP. 7. The possibility is considered that postaxotomy alterations in the electrical properties of motoneurons may explain these complex variations of mean EPSP amplitude and rise time.

Evidence of shared, direct input to motoneurons supplying synergist muscles in humans.

Cross-correlation techniques were used to test for the presence of shared, direct input to motoneurons innervating different synergist elbow flexor muscles in man. Motor unit activity was recorded intramuscularly from two elbow flexor muscles during steady isometric elbow flexion in normal and paretic subjects. To increase the probability of detecting weak synchrony, one of the intramuscular needles was positioned to record multiunit activity. Significant correlogram peaks were obtained in 25/57 runs in normal subjects, and the features of the correlograms were similar to those previously reported based on cross-correlation of two single units within the same muscle. Further, the characteristics of discharge synchrony measured in paretic stroke patients are consistent with other reports on the effects of stroke on synchrony among motoneurons belonging to the same pool, i.e. narrow correlogram peaks were rare in paretic subjects and significant correlogram peaks often had longer than normal durations.

Weakness in patients with hemiparesis.

Clinical and experimental results are reviewed concerning muscle weakness in patients with hemiparesis after a stroke. The discussion includes the important role that alterations in the physiology of motor units, notably changes in firing rates and muscle fiber atrophy, play in the manifestation of muscle weakness. This role is compared with the lesser role that spasticity (defined as hyperactive stretch reflexes) of the antagonist muscle group appears to play in determining the weakness of agonist muscles. The contribution of other factors that result in mechanical restraint of the agonist by the antagonist (e.g., passive mechanical properties and inappropriate cocontraction) is discussed relative to muscle weakness in patients with hemiparesis.

Abnormal spatial patterns of elbow muscle activation in hemiparetic human subjects.

The patterns of electromyographic (EMG) activity in spastic-paretic and contralateral elbow muscles of 10 hemiparetic human subjects were compared during a sequence of graded voluntary isometric contractions against 4 different-sized loads. These loads were orientated successively at 8 different angles over a 360 degree range, referenced to a plane at the wrist orthogonal to the long axis of the forearm. Comparisons of EMG activity recorded from normal and paretic limbs revealed that there were marked differences in the torque angles which evoked significant EMG activity, in the angular range of EMG, in the angle of peak EMG, and in the scaling of EMG magnitude with increasing isometric loads. In severely impaired limbs, there was a marked shift in both the peak EMG angle and the angular domain of EMG activity for both biceps and triceps muscle groups, away from the normal elbow flexion-extension axis towards external humeral rotation and shoulder girdle elevation. The extent of the disturbance in the spatial patterns of EMG activity was closely correlated with the clinical severity of the spastic-paretic disability, which was quantified using a functional scale patterned after that described by Fugl Meyer et al. (1975). The observed patterns of EMG activity in paretic flexor muscles do not conform with established synergistic patterns, such as might be released by excitation of the flexor reflex in a normal limb. Possible origins for the anomalous EMG patterns are discussed.

Partitioning of monosynaptic Ia excitatory postsynaptic potentials in the motor nucleus of the cat lateral gastrocnemius muscle.

Experiments were conducted to test the hypothesis that a partitioning of Ia monosynaptic excitatory postsynaptic potentials (Ia EPSPs) is present in motor nuclei supplying muscles with regions capable of different mechanical actions. Intracellular recordings of synaptic potentials were made in lateral gastrocnemius (LG) motoneurons in anesthetized low-spinal cats. The effects were tested of stimuli (group I range) to the four primary nerve branches of the LG nerve supplying muscle compartments LGm, LG1, LG2, and LG3 (terminology of English, Ref. 26) and the nerve to a heteronymous muscle, soleus. Stimulation of a given LG nerve branch produced monosynaptic Ia EPSPs of greater amplitude in "own-branch" motoneurons than "other-branch" cells. A significant partitioning of mean Ia EPSPs was found in three (LG1, LG2, LG3) out of the four homonymous pathways studied. An EPSP normalization (7) was performed to eliminate potential differences in cell type that might affect the amplitudes of the EPSPs between these four cell groups (e.g., differences in the number of cells supplying FF, FR, and S muscle units). This normalization confirmed that the partitioning of monosynaptic Ia inputs upon stimulation of LG1, LG2, and LG3 could not be attributed to differences in cell type. In addition, the effects of LGm stimulation were found to be significantly greater in the LGm motoneurons compared with the other cell groups. Heteronymous input (from soleus) to the LG motor nucleus showed some partitioned effects. Motoneurons innervating compartment LG2 received larger EPSPs from soleus than did the cells supplying compartments LG1, LG3, and LGm. The contributions of location specificity and species specificity (terminology of Scott and Mendell, Ref. 55) in the establishment of these Ia-afferent-motoneuronal connections were examined. Cell location sites within the spinal cord were consistent with location specificity making some contribution to the observed pattern of homonymous Ia connections. A more prominent role for species specificity was indicated by species-dependent differences in EPSP amplitude in pairs of LG motoneurons (e.g., LGm vs. LG2) at similar rostrocaudal locations upon stimulation of a given homonymous or heteronymous nerve/branch.

Partitioning of monosynaptic Ia excitatory post-synaptic potentials in the motor nucleus of the cat semimembranosus muscle.

In anaesthetized low-spinal cats, intracellular recordings were made of the Ia excitatory post-synaptic potential (e.p.s.p.) responses of semimembranosus motoneurones to electrical stimulation (Group I range) of nerve branches supplying the anterior and posterior heads of semimembranosus, the anterior and posterior parts of biceps femoris, and the distal part of semitendinosus. Recordings were also made during stimulation of nerves to the gracilis muscle and to the vasti muscle group. Stimulation of the semimembranosus-anterior nerve branch produced Ia e.p.s.p.s. of greater amplitude in semimembranosus-anterior motoneurones than in semimembranosus-posterior cells; likewise, stimulation of the semimembranosus-posterior nerve branch produced larger e.p.s.p.s. in cells which supplied the posterior head than in those which supplied the anterior head. Stimulation of the nerve branches to components of two 'flexor' muscles (Sherrington, 1910), biceps-posterior and semitendinosus-distal, produced larger e.p.s.p.s in semimembranosus-posterior cells than in the anterior motoneurones. A tendency was found for stimulation of the nerve to biceps femoris-anterior (an 'extensor') to produce larger e.p.s.p.s in semimembranosus-anterior than in-posterior motoneurones. However, this effect was of borderline (0.06 greater than P greater than 0.05) significance. The limited monosynaptic input produced by stimulation of the nerves to the gracilis and vasti muscles showed that their Ia axons do not distinguish between the two semimembranosus cell groups. A slight topographic organization of motoneurones within the semimembranosus motor nucleus was found, with anterior cells encountered, on average, at a more rostral level of the spinal cord than posterior cells. A similar topographic arrangement was observed in the rostrocaudal distribution of Group I afferent fibres in the dorsal roots and motor axons from the two sets of motoneurones in the ventral roots. These findings are consistent with 'location specificity' (Scott & Mendell, 1976) being a factor which contributes to the observed pattern of homonymous Ia connexions. A role for 'species specificity' (Scott & Mendell, 1976) in determining the observed pattern of homonymous Ia connexions was indicated by species-dependent differences in e.p.s.p. amplitude in pairs of semimembranosus-anterior and -posterior motoneurones at similar rostrocaudal locations in the spinal cord. The pattern of heteronymous connexions to the semimembranosus motor nucleus also showed evidence for species specificity. However, no clear topographic pattern was evident in these connexions.