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PubMed1990

Specific effects of retinoic acid on the skeletal morphogenesis of the 11-day mouse embryo forelimb bud in vitro.

Using our improved method for culturing 11-day mouse forelimb buds in vitro, we have investigated the effects of a local application of all-trans-retinoic acid (RA) on growth, cartilaginous differentiation and skeletal patterning in the mammalian limb bud. Carrier implants of catgut impregnated with DMSO or various doses of RA in DMSO were inserted at the apex of the buds in the proximo-distal axis just beneath the apical ectodermal ridge. After 6 days of culture, cartilaginous skeletons were stained and explants were processed for morphological analysis and quantitative study using computerized optical image analysis. Buds treated with low doses of RA exhibited stimulated growth and chondrogenesis. Moreover, hypertrophied and fused metacarpals were seen within explants treated with the lowest dose. High doses strongly inhibited growth and skeletal morphogenesis. An intermediate dose sustained cartilaginous differentiation at the same level as low doses, but concomitantly disturbed the skeletal pattern. These results are discussed considering reported RA effects on other experimental systems including avian limb bud as an in vivo model or cell cultures as an in vitro simplified model.

Animals↗
PubMed1984

Self-stimulation in the ventral tegmental area suppresses self-mutilation in rats with forelimb deafferentiation.

In rats which received section of 5 dorsal roots corresponding to the brachial plexus, self-mutilation of the forelimb develops during the first 2 months after deafferentation. The extent of self-mutilation was measured for 90 days in a control group of animals and in a group with an electrode implanted in the ventral tegmental area and which were allowed to self-stimulate at freedom. The animals which self-stimulated for 35 days did not develop the self-mutilation even after the self-stimulation was stopped.

Afferent Pathways↗
PubMed1984

Fictive locomotion of the forelimb evoked by stimulation of the mesencephalic locomotor region in the decerebrate cat.

Fictive locomotion, rhythmic nerve discharges mimicking locomotor activities, of the forelimb was found to be evoked by stimulation of the mesencephalic locomotor region (MLR), as that of the hindlimb, in immobilized decerebrate cats with the lower thoracic cord transected. The effective area for fictive locomotion was highly localized in the dorsolateral portion of the MLR, whereas a locomotor movement on the still belt of the treadmill was elicited from a slightly wider area and that on the moving belt from a further expanded area.

Animals↗
PubMed1987

Distribution of primary afferent fibres from the forelimb of the rat to the upper cervical spinal cord in relation to the location of spinothalamic neuron populations.

Half the monosynaptic spinothalamic neurons in the rat spinal cord lie in the first 4 cervical segments, predominantly in the internal basilar column and ventral horn. The present study shows that both these regions receive primary afferents from the forelimb. The superficial dorsal horn receives few, and the region of the lateral cervical nucleus no primary afferents from the brachial plexus. We suggest that internal basilar column cells may represent localised relays concerned with the limbs, and that the gracile and cuneate nuclei are not unique, but are paralleled by other neuron populations in the upper cord.

Animals↗
PubMed1989

Involvement of the substantia innominata/ventral pallidum complex in transmitting forelimb muscular rigidity evoked from the nucleus accumbens in rats.

In the present study it was investigated whether muscular rigidity elicited from the nucleus accumbens could be transmitted via the substantia innominata/ventral pallidum (SI/VP) complex. For this purpose rats were equipped with cannulae aimed at the nucleus accumbens and/or the SI/VP, and with electrodes in the triceps muscle of the forelimb. In the first set of experiments it was found that the GABA agonist muscimol (10-25 ng/0.5 microliters) dose-dependently increased tonic EMG activity upon injection into the SI/VP region. The GABA antagonist bicuculline (50 ng/0.5 microliters) antagonized the effects of muscimol (25 ng/0.5 microliters). In the second set of experiments it appeared that the increase in tonic EMG activity induced by haloperidol (1000 ng/0.5 microliters) injected into the nucleus accumbens was antagonized by subsequent injection of bicuculline (25 ng/0.5 microliters) into the SI/VP complex. These data suggest that the SI/VP complex may be one station through which the muscular rigidity elicited from the nucleus accumbens is transmitted to lower brain structures.

Animals↗
PubMed1990

Application of principal component analysis for characterizing convergence patterns of inputs in interneurones of the cat forelimb segments.

We attempted to quantitatively describe a variety of convergence patterns of inputs from peripheral nerves and descending tracts (13 sources) onto interneurones of the cat forelimb segments (C6-C8). To this end we applied principal component analysis using the latency of firing as the parameter of each input. The first 3 principal components thus obtained explained 65% of the total variance of convergence patterns and characterized the input pattern of each cell. The first principal component correlated mainly with inputs from pads and the median nerve, the second with the cortico- and rubro-spinal tracts and the third with the superficial radial nerve.

Animals↗
PubMed1991

Absence of recurrent axon collaterals in motoneurones to the extrinsic digit extensor muscles of the cat forelimb.

Forelimb alpha-motoneurones were intracellularly recorded in anaesthetized cats and iontophoretically filled with horseradish peroxidase (HRP). All motoneurones to the elbow flexors, elbow extensor and to the extensor carpi radialis muscles displayed in parallel homonymous recurrent inhibitory postsynaptic potentials (RIPSPs) and axon collaterals. Homonymous RIPSPs and axon collaterals were missing in the nuclei to the long digit extensor muscles. Two populations of motoneurones, with and without recurrent axon collaterals, seem to be present in the extensor carpi ulnaris motor nucleus. These results are consistent with the hypothesis that the motoneurones to the extrinsic digit extensors lack a recurrent axonal system. This indicates that the contribution of the recurrent Renshaw systems to motor control may be more complex than hitherto assumed.

Animals↗
PubMed1995

Skeletofusimotor (beta) innervation of proximal and distal forelimb muscles of the cat.

The innervation of muscle spindles by skeletofusimotor (beta) axons has been compared in two long digit extensor muscles with three elbow extensor muscles of the cat forelimb. The proportion of muscle spindle poles with p1-endplates was analysed in silver impregnated teased material. The proximal and distal muscles displayed a significant difference in their proportion of muscle spindle poles with p1-endplates. The distal muscles had an estimated proportion of more than 70% beta innervation of their muscle spindles, the proximal muscles of 41-47%. This difference is discussed with respect to the different circuitry of the motoneurones. We suggest that the high proportion of beta-innervated spindles in distal muscles obtained with the absence of a recurrent inhibitory system in the innervating motoneurones [18] serves the execution of manipulative movements.

Animals↗
PubMed1991

The effect of procaine injection into the medullary reticular formation on forelimb muscle activity evoked by mesencephalic locomotor region and vestibular stimulation in the decerebrated guinea-pig.

The effect of procaine microinjection into the ventromedial portion of the medullary reticular formation on forelimb muscle activity evoked by electrical mesencephalic locomotor region and natural vestibular stimulation has been investigated in the decerebrated guinea-pig. This injection is followed by a reversible increase of the threshold of mesencephalic locomotor region stimulation necessary for the activation of muscle rhythmic activity. Procaine injection is accompanied by reduction of vestibular influence on flexor muscle activity evoked by electrical cutaneous and mesencephalic locomotor region stimulation. Vestibular influence on extensor muscle activity remains unchanged after the injection. The results indicate that medial medullary reticular formation is the site of the convergence of mesencephalic locomotor region and vestibular activity. It is suggested that the vestibular system contributes to the modulation of reticulospinal activity coupled with the initiation and control of locomotion.

Animals↗
PubMed1994

Differential contribution of motor cortex and caudate nucleus to instrumental tongue-forelimb synchronization in rats: a functional ablation study.

The functional ablation technique was used to assess the role of motor cortex and caudate nucleus in a complex skilled movement. Rats were trained to synchronize tongue and forepaw movements in a drinking box equipped with a retractable spout which was automatically withdrawn after every lick but could be returned by pressing and releasing a lever placed 4 cm below the spout. The animals learned to perform short presses synchronized with the lick cycle in such a way as to allow continuous drinking. Neural circuits implementing these lick-associated instrumental movements were blocked by intracranial injection of 10 ng of tetrodotoxin. Bilateral blockade of the motor cortex interfered with lick-synchronized bar pressing, but did not significantly influence licking from a stationary spout. Both licking and bar-pressing were impaired by bilateral injection of tetrodotoxin into the lateral part of the caudate nucleus for the duration of the tetrodotoxin-induced inactivation of the target region. The instrumental tongue-forelimb synchronization recovered considerably later, i.e. after two to three days. Functional blockade of the medial part of the caudate nucleus caused only a partial impairment of lick-synchronized bar pressing lasting less than 7 h and did not significantly influence consummatory licking. It is concluded that the tongue-forepaw synchronization is disrupted by blockade of motor cortex or lateral caudate considerably longer than the performance of the isolated component movements.

Animals↗
PubMed1995

Effects of complete and partial lesions of the dopaminergic mesotelencephalic system on skilled forelimb use in the rat.

This study compares certain behavioural consequences of partial and complete unilateral lesions of the dopaminergic mesotelencephalic system. We investigated skilled forelimb use, rotations induced by apomorphine and amphetamine, and dopaminergic metabolism of the nigrostriatal system of rats that had received a unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. The rats classified Apo(+), that rotated after the administration of apomorphine, had a complete lesion of the nigrostriatal system, whereas those classified Apo(-), that did not rotate after the administration of apomorphine, had a partial lesion of the nigrostriatal system. In the Apo(+) rats, 99.8% of the dopamine in the striatum was depleted, as was 85% of that in the substantia nigra. For the Apo(-) rats, 72% of the dopamine in the striatum was depleted as was 56% of that in the substantia nigra. When investigated with the staircase test, the animals with the most severe dopamine depletions were those most impaired in the paw reaching task. Complete and partial unilateral depletions of the dopaminergic mesotelencephalic system impaired the hierarchic phases of paw reaching differently. A complete dopamine depletion, but not a partial one, decreased the number of attempts made with the contralateral paw, and induced a bias towards the ipsilateral paw. A partial dopamine lesion impaired the sensorimotor co-ordination of both paws, whereas the complete dopamine lesion had a greater effect on the contralateral paw than on the ipsilateral paw. The mild paw reaching impairments observed in animals with moderate depletions of dopamine are proposed as a model of the early symptoms of Parkinson's disease that may be useful for the development of protective or restorative therapies.

Animals↗
PubMed2004

The effects of intracortical endothelin-1 injections on skilled forelimb use: implications for modelling recovery of function after stroke.

Different methods of inducing experimental brain lesions can result in distinct neuropathological sequelae. This could be of consequence in attempts to establish animal models of recovery of function following stroke, as differences in the progression of experimental lesion pathology may have an impact on the magnitude and rate of recovery of function observable with any particular lesioning method. In the present study, a novel method of producing a focal ischaemic lesion by intracortical microinjection of endothelin-1 (ET-1) was compared with excitotoxic (microinjection of quinolinic acid) and mechanical (aspiration) lesioning procedures. Lesions were unilateral and were targeted at the forelimb representation zone in sensorimotor cortex. It was found that all three types of lesion had an essentially identical effect with regard to reaching accuracy in a paw-reaching task. All lesioned animals displayed a similar, significant long-term deficit in reaching accuracy and limited degree of recovery relative to sham animals. Off-line analysis of the performance of animals during post-lesion week 9 indicated that animals in each lesion group also displayed a similar deficit. The current results suggest that the spontaneous behavioural consequences of a unilateral lesion of FL in the rat appear to be independent of the nature of lesion production. However, the increased face validity of an ET-1-induced lesion, coupled with the ease of control of lesion placement and extent offered by this technique make for a potentially important animal model for research into drug effects on recovery of function following stroke.

Animals↗
PubMed2006

Energetics of swimming by the ferret: consequences of forelimb paddling.

The domestic ferret (Mustela putorius furo) swims by alternate strokes of the forelimbs. This pectoral paddling is rare among semi-aquatic mammals. The energetic implications of swimming by pectoral paddling were examined by kinematic analysis and measurement of oxygen consumption. Ferrets maintained a constant stroke frequency, but increased swimming speed by increasing stroke amplitude. The ratio of swimming velocity to foot stroke velocity was low, indicating a low propulsive efficiency. Metabolic rate increased linearly with increasing speed. The cost of transport decreased with increasing swimming speed to a minimum of 3.59+/-0.28 J N(-1) m(-1) at U=0.44 m s(-1). The minimum cost of transport for the ferret was greater than values for semi-aquatic mammals using hind limb paddling, but lower than the minimum cost of transport for the closely related quadrupedally paddling mink. Differences in energetic performance may be due to the amount of muscle recruited for propulsion and the interrelationship hydrodynamic drag and interference between flow over the body surface and flow induced by propulsive appendages.

Animals↗
PubMed2005

Dietary supplementation of omega-3 polyunsaturated fatty acids worsens forelimb motor function after intracerebral hemorrhage in rats.

Dietary intake of omega-3 polyunsaturated fatty acids has been associated with decreased clotting ability and increased risk of hemorrhagic stroke. The aim of the current study was to assess the effect of dietary supplementation of omega-3 polyunsaturated fatty acid on functional outcome after hemorrhagic stroke. Rats were maintained on a diet containing approximately 30% of energy as either fish oil (rich in omega-3 fatty acids) or safflower oil (rich in omega-6 fatty acids) and subjected to either intracerebral hemorrhage or sham surgery. Behavioral tests, infarct measurement, and MR imaging techniques were used to assess outcome. While there was no significant difference in infarct volume between rats on different diets, animals maintained on a diet enriched with fish oil exhibited increased cerebral blood flow after surgery. These animals were significantly more impaired than rats fed the safflower-oil-enriched diet in tests of forelimb dexterity and fine motor control. These results suggest that high intake of omega-3 polyunsaturated fatty acids may not only increase the risk of hemorrhagic stroke as shown in previous studies, but most importantly may lead to a more severe motor impairment and a poorer functional outcome after such an event.

Animals↗
PubMed2005

Adult rat forelimb dysfunction after dorsal cervical spinal cord injury.

Repairing upper extremity function would significantly enhance the quality of life for persons with cervical spinal cord injury (SCI). Repair strategy development requires investigations of the deficits and the spontaneous recovery that occurs when cervical spinal cord axonal pathways are damaged. The present study revealed that both anatomically and electrophysiologically complete myelotomies of the C4 spinal cord dorsal columns significantly increased the adult rat's averaged times to first attend to adhesive stickers placed on the palms of their forepaws at 1 week. Complete bilateral myelotomies of the dorsal funiculi and dorsal hemisection, but not bilateral dorsolateral funiculi injuries, also similarly increased these times at 1 week. These data extend a previous finding by showing that a forepaw tactile sensory deficit that occurred in the adult rat after bilateral C4 spinal cord dorsal funiculi injury is due to damage of the dorsal columns. Averaged times to first attend to the stickers also decreased to those of sham-operated rats at 3 and 4 weeks post-dorsal hemisection with weekly testing. In contrast, a separate group of rats with dorsal hemisections had significantly increased times when tested only at 4 weeks. These data indicate that frequent assessment of this particular behavior in rats with dorsal hemisections extinguishes it and/or engenders a learned response in the absence of sensory axons in the dorsal columns and dorsolateral funiculi. This finding contrasted with weekly testing of grid walking where increased forelimb footfall numbers persisted for 4 weeks post-dorsal hemisection.

Afferent Pathways↗
PubMedDate not supplied

Cadmium-induced postaxial forelimb ectrodactyly: association with altered sonic hedgehog signaling.

Administration of CdSO(4) to C57BL/6 mice at day 9.5 of gestation induces a high incidence of postaxial forelimb ectrodactyly in the offspring. We propose that Cd(2+) exposure impairs the process of anterior/posterior formation in the limb bud, a process that is directed by Sonic hedgehog (Shh) signaling. We show that exposure of the mouse embryo to Cd(2+) disrupts Shh signaling as measured by polarizing activity of mouse limb bud ZPA grafted to a host chick wing, and activity of a Gli:luciferase reporter exposed to limb bud lysates. Yet the expression of Shh and its translation are not affected by Cd(2+) exposure. We propose that teratogen exposure affects the processing of Shh in the cells in which it is made.

Animals↗
PubMed2004

The effects of extracorporeal shock-wave therapy on the ultrasonographic and histologic appearance of collagenase-induced equine forelimb suspensory ligament desmitis.

Extracorporeal shock-wave therapy (ESWT) may stimulate healing of desmitis in multiple species. The objective of this study was to evaluate the ultrasonographic and histologic appearance of collagenase-induced suspensory ligament (SUL) desmitis in untreated ligaments and ligaments treated with ESWT in horses. Four mature horses had SUL desmitis induced in both forelimbs. Beginning 3 weeks after induction of the lesions, one ligament per horse was treated 3 times at 3-week intervals with ESWT. The percent lesion, echogenicity and fiber alignment scores of the SULs were evaluated at 3-week intervals for a total of 15 weeks. At the completion of the study, the horses were euthanized and the SULs collected, fixed and processed for histopathologic evaluation. Ultrasonography showed treated SULs had a smaller percent lesion at the maximal injury zone (p = 0.001), and the total percent lesion (p = 0.01), total fiber alignment score (p = 0.0167) and total echogenicity (p = 0.0023) were all smaller in the treated ligaments. The fiber alignment score and echogenicity were not statistically different at the maximal injury zone. The treated SULs had a more concentrated area of metachromasia associated with healing than the untreated ligaments, where metachromasia appeared more diffuse throughout the ligament. ESWT improved the rate of healing as assessed ultrasonographically.

Animals↗
PubMed2001

Stimulus time-locked responses of motoneurons during forelimb fictive locomotion evoked by repetitive stimulation of the lateral funiculus.

In cat forelimb fictive locomotion evoked by repetitive stimulation of the upper cervical lateral funiculus, locomotor discharges consisted of activities time-locked to each stimulus, which were rhythmically modulated. The stimulus time-locked activities were investigated by intracellular recording from motoneurons. In both elbow flexor and extensor motoneurons, there observed stimulus time-locked disynaptic EPSPs, trisynaptic IPSPs and polysynaptic EPSPs, all of which were rhythmically modulated with specific patterns. The disynaptic EPSPs of flexor motoneurons were facilitated in the flexor phase of locomotion, whereas those of extensor motoneurons were facilitated from the flexor phase to the flexor-to-extensor transition phase. Modulation depth was larger in flexor motoneurons. Trisynaptic IPSPs changed in amplitude in parallel with the disynaptic EPSPs of the antagonistic motoneurons. Late, polysynaptic EPSPs of both flexor and extensor motoneurons increased in amplitude along with corresponding nerve discharges. After lesions of the lateral funiculus at C6/C7, both the disynaptic EPSPs and trisynaptic IPSPs were abolished in the motoneurons located caudally to the lesions. However, only trisynaptic IPSPs were lost in the rostrally located motoneurons. Furthermore, the lesions disclosed that extensor motoneurons received another kind of stimulus time-locked EPSPs, trisynaptic EPSPs, which were transmitted through the ventral part of the spinal cord, and rhythmically facilitated in the extensor phase. Stimulus time-locked PSPs observed in this study may at least in part be evoked by last-order interneurons of the central pattern generator, which may be reciprocally organized.

Action Potentials↗