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Differential effects of aging on motoneurons and peripheral nerves innervating the hindlimb and forelimb muscles of rats.

We examined the number and size of ulnar (forelimb) and medial gastrocnemius (MG, hindlimb) motoneurons in middle-aged (9 months of age) and aged (27 months of age) male Fischer 344 rats. Morphological properties of the ulnar and the MG nerves were also studied. No significant difference was found in the mean number of the ulnar motoneurons between the two age groups, while that of MG motoneurons was significantly less in aged animals. A decrease in the number of myelinated fibers (including both afferent and efferent fibers) in the ulnar nerves was less than that in the MG nerves, although the age difference was not significant in either of the nerves. Soma atrophy of aged motoneurons was found in both MG and ulnar motor nuclei. The mean fascicular areas and myelinated fiber diameters were significantly increased in both the MG and the ulnar nerves in aged rats, but these were less pronounced for the ulnar nerve. The results indicate that most ulnar motoneurons, unlike MG motoneurons, survive at least to the age of 27 months. Morphological changes in the peripheral nerves were also less for the ulnar nerve than for the MG nerve. Thus, we conclude that the effects of aging on motoneurons and peripheral nerves innervating MG muscle of the hindlimb are greater than those innervating forelimb muscles.

Aging↗

Increase of extensor tonus of forelimbs in chronic cats with bilateral serial hemisections of the spinal cord at different levels.

An increase of extensor tonus of the forelimbs was observed in chronic cats with serial double hemisections of the spinal cord, first at a lower thoracic level followed by a contralateral hemisection at the midthoracic cord at intervals of 5-18 weeks. A similar increase in forelimb extensor tonus was observed in chronic cats with serial double hemisections, first at the high cervical cord followed by a contralateral hemisection of the mid-thoracic cord at intervals of 3-7 weeks. The results suggest that the augmentation of extensor tonus was brought about by release of bulbar centers from ascending inhibitory mechanisms from the lower spinal cord.

Animals↗

Representation of forelimb mechanoreceptors within the superior colliculus of the cat.

Forelimb mechanoreceptor representation within the superior colliculus was investigated using microelectrode recording in decerebrate or anaesthetized cats. Selective activation of different mechanoreceptive fibre classes supplying the distal forelimb revealed a poor representation of all three fibre classes (SA, PC and RA) that innervate the glabrous skin. Furthermore, there was no evidence for Pacinian (PC) input from the interosseous or wrist region. The tap stimuli which are often needed to activate the collicular neurones, may be effective, when applied to the distal limb, because of stimulus spread to more proximal sites, or as a result of the synchronous recruitment of multiple classes of afferent fibres.

Animals↗

Restoration of complex sensorimotor behavior and skilled forelimb use by a modified nigral cell suspension transplantation approach in the rat Parkinson model.

While intrastriatal transplants of dopamine-rich ventral mesencephalic tissue are effective in reversing a variety of drug-induced behaviors in the rat Parkinson model, previous studies have failed to obtain significant graft-induced effects on deficits in certain aspects of complex sensorimotor behaviors. In the present study we have applied a modified cell suspension transplantation procedure, which allows more reproducible and consistent ventral mesencephalic transplants of large size, as well as more wide-spread distribution of the ventral mesencephalic tissue over multiple graft sites within the denervated caudate-putamen. Using this approach it has for the first time been possible to obtain significant amelioration of the lesion-induced deficits in skilled forelimb use and in the rats ability to switch from one behavior (eating) to another (orientation towards tactile stimuli), so-called disengage behavior. Rats with unilateral 6-hydroxydopamine lesions of the mesostriatal dopamine pathway received a total of 450,000 fetal ventral mesencephalic cells, implanted either as two large deposits along a single injection tract ("Macro" grafts), or as 18 small deposits along six injection tracts in the head of the denervated caudate-putamen ("Micro" grafts) and the behavioral changes were studied up to three months after transplantation. On the drug-induced tests, both types of transplants reversed amphetamine- and D1-receptor agonist-induced turning, and produced a partial (50-75%) reduction in apomorphine-induced and D2-receptor agonist-induced turning. On the spontaneous sensorimotor tests, both types of grafts reversed the deficit in simple sensorimotor orientation. In addition, the Micro-grafted animals (which produced the most extensive reinnervation of the denervated striatum) showed a significant improvement in skilled forelimb use and in response latency in the disengage behavior test. Although the large sized Macro-grafted animals showed a similar trend, it did not reach significance. Moreover, the Micro grafts had a more pronounced effect on spontaneous turning behavior in a conditioned response test. The improvement in response latency in the disengage test was significantly correlated with the dopamine level in the nucleus accumbens, whereas the magnitude of the conditioned turning response was significantly correlated with the dopamine levels in the head of the caudate-putamen. The results show that intrastriatal nigral transplants, despite their ectopic placement, can ameliorate lesion-induced deficits also in more complex sensorimotor behaviors. This improved graft effect is likely to depend on both extensive dopaminergic reinnervation throughout the head of the caudate-putamen, as well as on closer integration of the grafted nigral tissue with the host striatal circuitry.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Transplants of embryonic cortical tissue placed in the previously damaged frontal cortex of adult rats: local cerebral glucose utilization following execution of forelimb movements.

Transplantation of fetal cortical tissue into the motor cortex of adult rats was used as an experimental model to examine the functional integration of homotopic fetal neocortical grafts into the motor pathways of adult host brain. We have employed the [14C]2-deoxy-D-glucose method to analyse the metabolic activity of the transplant and host sensorimotor cortex: (i) in animals solicited to perform specific lever-pressing movements with the limb contralateral to the transplant (experimental group); and (ii) in non-solicited animals or in animals using the limb ipsilateral to the transplant (control group). Grafts in the control group displayed homogeneous uptake of 2-deoxy-D-glucose throughout the rostrocaudal extent of the transplant. The local cerebral glucose utilization levels were low as compared to those of the surrounding cortex but were at least two-times higher than in the corpus callosum. Increase in 2-deoxy-D-glucose uptake by the transplant cells was found only in the experimental group. In this group, 2-deoxy-D-glucose uptake was higher in the caudal (AP: +3.0 to +1.7 mm, relative to Bregma) than in the rostral sectors of the transplants suggesting the existence of a topographic organization within the transplant. In addition, except in the rostral part, glucose utilization was higher in the transplant of the experimental group than in the sensorimotor areas of the non-activated cortex in the control group. Moreover, glucose utilization of the transplant cells was systematically higher in the experimental than in the control group. The transplants appear to display a certain level of metabolic integration with the host sensorimotor cortex since, in the experimental group, there was no significant differences in local cerebral glucose utilization values in the caudal sector of the transplant and in the surrounding sensorimotor cortical areas of the host. The 2-deoxy-D-glucose uptake was even higher in the caudal sector of the transplant than in some of the subfields of the contralateral sensorimotor cortex. The present findings indicate for the first time that motor activation of the contralateral forelimb produces an increase in metabolic activity in distinct transplant sectors, the topographic distribution of which matches the normal topographic organization of the forelimb somatomotor map. This suggests that transplants of embryonic frontal neocortex placed in the frontal cortex of adult hosts become functionally integrated with the host motor system.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Ipsilateral motor control of the forelimb in the congenitally acallosal mouse.

The corticospinal projections of mice with callosal agenesis were investigated using electro-physiological and horseradish peroxidase techniques. In the normal mouse, intracortical stimulation of the motor area with the microelectrode resulted in contralateral contraction of the forelimb, whereas ipsilateral contraction was observed in the acallosal mouse. Hence, mice with congenital absence of the corpus callosum show physiologically ipsilateral motor control. Furthermore, latency of the forelimb contraction elicited by electrical stimulation of the acallosal mouse was slightly shorter than that of the normal mouse. On the other hand, it was confirmed by a horseradish peroxidase technique that the corticospinal tract and peripheral motor neurons in the spinal cord of the acallosal mouse were identical to those of the normal mouse.

Agenesis of Corpus Callosum↗

Contralesional neural plasticity and functional changes in the less-affected forelimb after large and small cortical infarcts in rats.

Some studies have found that unilateral cerebral damage produces significant deficits in the ipsilesional, "less-affected", body side. Other studies have found that such damage results in a paradoxical hyperfunctionality of the ipsilesional body side and a facilitation of learning-induced neuroplastic changes in the contralesional motor cortex. The purpose of this study was to determine whether these effects co-exist and/or vary with lesion severity. After small or large unilateral ischemic lesions of the sensorimotor cortex (SMC) or sham operations, adult male rats were trained for 20 days to acquire a motor task, skilled reaching for food, for the first time with the ipsilesional forelimb. Analyses of movement patterns indicated lesion-size-dependent ipsilesional abnormalities in grasping, retrieving and releasing food pellets. Despite these impairments, success rates were significantly increased and aiming errors reduced in lesion groups compared with sham operates. Performance was best in rats with small lesions that had more minor ipsilesional impairments. In the motor cortex contralateral to the lesion and trained limb, there were significant increases in the density of dendrites immunoreactive for microtubule-associated protein-2 (MAP2) and of N-methyl-D-aspartate receptor subunit 1 (NMDAR1) immunoreactivity compared with sham operates. These effects were correlated with reaching performance. Therefore, enhanced motor skill learning in the "less-affected" forelimb and contralesional neuroplastic changes are muted after larger lesions and co-exist with ipsilesional impairments. These effects may be related to a denervation-induced neural restructuring of the contralesional cortex that both disrupts pre-existing motor engrams and facilitates the establishment of new ones.

Animals↗

Passive and active mechanical properties of the superficial and deep digital flexor muscles in the forelimbs of anesthetized Thoroughbred horses.

The superficial (SDF) and deep digital flexor (DDF) muscles are critical for equine forelimb locomotion. Knowledge of their mechanical properties will enhance our understanding of limb biomechanics. Muscle contractile properties derived from architectural-based algorithms may overestimate real forces and underestimate shortening capacity because of simplistic assumptions regarding muscle architecture. Therefore, passive and active (=total - passive) force-length properties of the SDF and DDF muscles were measured directly in vivo. Muscles from the right forelimbs of four Thoroughbred horses were evaluated during general anesthesia. Limbs were fixed to an external frame with the muscle attached to a linear actuator and load cell. Each muscle was stretched from an unloaded state to a range of prefixed lengths, then stimulated while held at that length. The total force did not exceed 4000 N, the limit for the clamping device. The SDF and DDF muscles produced 716+/-192 and 1577+/-203 N maximum active isometric force (F(max)), had ascending force-length ranges (R(asc)) of 5.1+/-0.2 and 9.1+/-0.4 cm, and had passive stiffnesses of 1186+/-104 and 1132+/-51 N/cm, respectively. The values measured for F(max) were much smaller than predicted based on conservative estimates of muscle specific tension and muscle physiological cross-sectional area. R(asc) were much larger than predicted based on muscle fiber length estimates. These data suggest that accurate prediction of the active mechanical behavior of architecturally complex muscles such as the equine DDF and SDF requires more sophisticated algorithms.

Algorithms↗

Oscillatory activity in forelimb muscles of behaving monkeys evoked by microstimulation in the cerebellar nuclei.

Coherent 20-35 Hz (beta) oscillations are a prominent feature of activity in primary motor cortex and muscles of monkeys and humans performing voluntary movements. We found that coherent beta oscillations are also present in the cerebellar nuclei (CN). Two monkeys were operantly conditioned to perform a wrist flexion/extension step-tracking task while we recorded neuronal activity or microstimulated in CN and recorded EMG activity from forelimb muscles. Coherent beta oscillations were found between discharges of some CN neurons and tonically active shoulder, elbow and wrist/finger flexion and extension muscles. Similarly, localized microstimulation pulses in CN evoked transient beta oscillations in widespread forelimb muscles. We conclude that coherent motor system beta oscillations are present in CN and that CN may be an important nodal point for the generation and/or propagation of beta oscillations throughout the motor system.

Action Potentials↗

Lack of topographic specificity in nerve fiber regeneration of rat forelimb mixed nerves.

Multiple nerve repair by means of a Y-shaped nerve guide represents a good model for studying the specificity of peripheral nerve fiber regeneration. Here we have used it for investigating the specificity of axonal regeneration in mixed nerves of the rat forelimb model. The left median and ulnar nerves, in adult female rats, were transected and repaired with a 14-mm Y-shaped conduit. The proximal end of the Y-shaped conduit was sutured to the proximal stump of either the median nerve or the ulnar nerve. Ten months after surgery, rats were tested for functional recovery of each median and ulnar nerve. Quantitative morphology of regenerated myelinated nerve fibers was then carried out by the two-dimensional disector technique. Results showed that partial recovery of both median and ulnar nerve motor function was regained in all experimental groups. Performance in the grasping test was significantly lower when the ulnar nerve was used as the proximal stump. Ulnar test assessment showed no significant difference between the two Y-shaped repair groups. The number of regenerated nerve fibers was significantly higher in the median nerve irrespectively of the donor nerve, maintaining the same proportion of myelinated fibers between the two nerves (about 60% median and 40% ulnar). On the other hand, nerve fiber size and myelin thickness were significantly larger in both distal nerves when the median nerve was used as the proximal donor nerve stump. G-ratio and myelin thickness/axon diameter ratio returned to normal values in all experimental groups. These results demonstrate that combined Y-shaped-tubulization repair of median and ulnar nerves permits the functional recovery of both nerves, independently from the proximal donor nerve employed, and that tissue, and not topographic, specificity guides nerve fiber regeneration in major forelimb mixed nerves of rats.

Animals↗

Compensatory load redistribution of horses with induced weight-bearing forelimb lameness trotting on a treadmill.

The study was performed to obtain a detailed insight into the load and time shifting mechanisms of horses with unilateral weight-bearing forelimb lameness. Reversible lameness was induced in 11 clinically sound horses by applying a solar pressure model. Three degrees of lameness (subtle, mild and moderate) were induced and compared with sound control measurements. Vertical ground reaction force-time histories of all four limbs were recorded simultaneously on an instrumented treadmill. Four compensatory mechanisms could be identified that served to reduce structural stress, i.e. peak vertical force on the affected limb: (1) with increasing lameness, horses reduced the total vertical impulse per stride; (2) the diagonal impulse decreased selectively in the lame diagonal; (3) the impulse was shifted within the lame diagonal to the hindlimb and in the sound diagonal to the forelimb; (4) the rate of loading and the peak forces were reduced by prolonging the stance duration. Except in the diagonal hindlimb, where peak vertical forces increased slightly in the moderate lameness condition, no equivalent compensatory overload situation was observed in the other limbs. Specific force and time information of all four limbs allow the unequivocal identification of the affected limb.

Adaptation, Physiological↗

Quantitative analyses of thalamic and cortical origins of neurons projecting to the rostral and caudal forelimb motor areas in the cerebral cortex of rats.

On the basis of studies using intracortical microstimulation, the existence of rostrocaudally separate two forelimb representation areas has been inferred in the motor cortex of rats. They are termed caudal and rostral forelimb areas (CFA and RFA). In this study, it was confirmed first that RFA and CFA are located in cytoarchitectonically distinct areas (medial and lateral parts of agranular cortex, respectively). In the second part of this study, the distribution of thalamic and cortical neurons projecting to RFA and CFA was quantitatively compared by injections of small and relatively constant amounts of retrograde fluorescent dyes (diamidino yellow and fast blue) into these areas. It was observed that (1) main inputs to RFA originated from AGl, namely CFA (2) CFA received dominant inputs from AGm including RFA and caudally adjacent granular cortex and (3) wider cortical areas and larger number of neurons projected to CFA than to RFA. As for the thalamocortical projections, both RFA and CFA received inputs from various thalamic nuclei, such as VL, VM, Po, PC, PF, CL, but cells projecting to RFA and CFA were differentially located in each nucleus. It was found that labeled cell number and/or density in VM, PC, CL, CM and MD after RFA injections were significantly larger than those after CFA injections. On the other hand, labeled cell number and/or density in VPL and VL were significantly higher after CFA injections than after RFA injections. In comparison with findings in primates, the results suggest that the cortical motor areas of rats may be specialized for different aspects of motor control.

Animals↗

Shoulder and forelimb orientations and loading in sitting cats: implications for head and shoulder movement.

A three-dimensional static analysis was carried out to characterize the effects of ground reaction forces propagated through different joints in the forelimb and shoulder of quietly sitting cats. Stereofluoroscopy, used to identify the orientations of bones, showed that the scapula is held in a parasagittal plane, with its vertebral border located dorsally to the spines of thoracic vertebrae. The forelimb is held with the elbow flexed. Loading on the elbow tended to flex and adduct the ulna, whereas loading on the glenohumeral joint tended to extend, adduct and internally rotate the humerus. Loading on the scapula was confined primarily to the sagittal plane and tended to rotate the vertebral border of the scapula caudally around the head of the humerus. This caudally-directed moment suggests that the static equilibrium of the feline scapula depends upon muscular forces directed cranially, presumably by way of attachments on the skull and cervical column. The differing arrangement of the shoulder-to-neck transition in cats and humans suggests caution in the use of feline models to represent some aspects of human head movement.

Animals↗

On the origin of skilled forelimb movements.

Homologizing behaviour was once considered unreliable, but the application of modern comparative methods has been shown to provide strong evidence of behavioural homologies. Skilled forelimb movements were thought to originate in the primate lineage but in fact are common among tetrapod taxa and probably share a common origin in early tetrapods. Furthermore, skilled movements are likely to have been derived from, and elaborated through, food-handling behaviour. In addition, it is now thought that the role played by the lateral and medial descending pathways of the spinal cord in the execution of skilled forelimb movements could be synergistic, rather than the exclusive responsibility of an individual pathway.

Animals↗

Does endogenous progesterone promote recovery of chronic sensorimotor deficits following contusion to the forelimb representation of the sensorimotor cortex?

We studied sensorimotor recovery in male, normal-cycling and pseudopregnant female rats following unilateral FL-SMC contusions. Forelimb use (push off before a rear, support against the walls, and landing after a rear) and the foot fault test (foot misplacements during locomotion on an elevated grid) were analyzed from videotapes taken before surgery, and then again on post-surgical days 2 and 36. High endogenous progesterone levels in females at the time of injury did not affect recovery as there were no differences between males, pseudopregnant females and normal-cycling female rats on these behaviors. None of the brain-injured rats recovered symmetrical forelimb use between 2 and 36 days after injury (P>0.05) and they also showed foot misplacements (P>0.05) in the foot fault test. Male and female rats with contusions had fewer mean foot misplacements on day 36 than 2 days after injury (P<0.001), indicating that there was partial recovery on this task. These results were taken to show that there were no sex differences in motor deficits caused by unilateral FL-SMC injury. In addition, higher endogenous progesterone levels in females did not protect them from the chronic sensorimotor deficits caused by unilateral FL-SMC contusions.

Animals↗

Utilization of the Denny-Brown collection: differential recovery of forelimb and hind limb stepping after extensive unilateral cerebral lesions.

The Denny-Brown collection of primate lesion material was used to test the hypothesis that there is a difference in the rate of forelimb and hind limb recovery of locomotor movements after major unilateral cerebral ablation (pre/postcentral gyrus, decortication or hemispherectomy). The results indicate that, following major cerebral injury, hind limb recovery precedes that of the forelimb in adolescent and adult primates, but not in infants. This suggests that there is an underlying physiological basis to the widely-held belief that, in humans, lower limb recovery after stroke is generally more complete than that of the upper limb.

Aging↗

Forelimb lameness in the young patient.

Forelimb lameness is a common problem in young dogs and can be caused by a wide variety of problems. Accurate and comprehensive diagnosis and treatment must be provided for these patients. Differential diagnoses for forelimb lameness in the young patient fall into the categories of congenital abnormalities; developmental disorders; trauma; and infectious, nutritional, metabolic, and neoplastic causes. The etiopathogeneses of many of these disorders are still unknown, and treatment options and prognoses vary tremendously. Until definitive causes are determined, it is the responsibility of veterinarians to address the factors that contribute to the development and progression of these disorders. These areas primarily involve weight and nutritional management as well as breeding programs.

Animals↗

Effects of pyramidal tract stimulation on forelimb flexor motoneurons during fictive locomotion in cats.

To investigate spinal mechanisms of control of locomotion by the pyramidal system, we made intracellular recording from forelimb flexor motoneurons, and analyzed excitatory postsynaptic potentials (EPSPs) evoked by stimulation of the medullary pyramid during forelimb fictive locomotion in immobilized, decerebrate cats. We observed that (1) pyramidal stimulation evoked disynaptic EPSPs, (2) which were much bigger in the locomotor state than in the resting state, and that (3) the pyramidal EPSPs were rhythmically modulated, so that the facilitation occurred in the flexor-active phase. Last-order neurons mediating pyramidal effects presumably receive rhythmic input from the spinal locomotor network.

Animals↗