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PubMed1991

The effect of administration time on malformations induced by three anticonvulsant agents in C57BL/6J mice with emphasis on forelimb ectrodactyly.

Exposure of C57BL/6J mice to three anticonvulsant derivatives, namely, dimethadione, sodium valproate, and sodium diphenylhydantoin, each induced postaxial forelimb ectrodactyly. The agents were administered at gestational days 9, 9 1/3, 9 2/3, and 10. It was determined that administration at day 9 2/3 induced the highest percentage of forelimb ectrodactyly for each of the three agents. The forelimb ectrodactyly response in the C57BL/6J strain was compared with the A/J strain (Collins et al., Teratology, 41:61-70, 1990); it was found that the C57BL/6J strain was more sensitive to dimethadione and the A/J strain was more sensitive to diphenylhydantoin and sodium valproate. The position of vertebral defects induced by sodium valproate correlated with the time of drug administration. The overall syndrome of malformations induced by the three anticonvulsant agents was relatively similar in the two mouse strains and differed between each of the anticonvulsant agents.

Abnormalities, Drug-Induced↗
PubMed1993

Correlation of forelimb malformation asymmetries with visceral organ situs in the transgenic mouse insertional mutation, legless.

We studied the relationship between the sidedness of visceral organs and the expression of limb abnormalities in the legless mutant. The control of asymmetry in visceral development appears to be random in the legless mutant; that is, 50% develop normally (situs solitus) and 50% develop with inverted viscera (situs inversus). We find that the sidedness of forelimb abnormalities expressed in the mutants is highly correlated with visceral sidedness. Abnormalities are more severe in the right forelimbs in situs solitus mutants, while the left forelimb is more severely affected in situs inversus mutants.

Animals↗
PubMed2000

Identification of a murine locus conveying susceptibility to cadmium-induced forelimb malformations.

The heavy metal cadmium (Cd), an environmentally ubiquitous contaminant, is a potent teratogen in mice. When administered parenterally, it induces an array of malformations that vary in scope and severity with the route, dose, time of administration, and the strain of the animal. When administered intraperitoneally on day 9.0 of gestation, 4 mg/kg cadmium chloride produces forelimb defects (predominantly ectrodactyly) in over 80% of fetuses of the C57BL/6 mouse strain, while no limb defects are observed in the identically treated SWV strain. Like other examples of strain-specific teratogenic activity, the underlying nature of the differential susceptibility remains unknown. The present study investigates the segregation of sensitivity to Cd-induced forelimb defects in crosses between C57BL/6 and SWV mice and provides evidence for the involvement of both maternal and fetal factors in the determination of defect expression. In addition, quantitative trait loci (QTL) analysis of the fetal genetic component was performed among 198 backcross progeny, utilizing a genomic linkage map of 149 informative microsatellite markers. One QTL demonstrating significant linkage to expression of the defect, designated Cadfar (cadmium-induced forelimb autopod reduction), was mapped to the distal end of chromosome 6 with a lod score of 3.1.

Abnormalities, Drug-Induced↗
PubMed1990

Axonal projection of descending pathways responsible for eliciting forelimb stepping into the cat cervical spinal cord.

The descending pathways responsible for eliciting forelimb stepping are located in the lateral funiculus (Yamaguchi 1986). In order to determine into which spinal segments the descending pathways project and to know the projections and functions of the other descending system, the ventral funicular pathways, we placed various lesions in the cervical spinal cord of decerebrate cats with the lower thoracic cord transected and studied their effects on forelimb stepping evoked by stimulation of the midbrain locomotor region. (1) The lateral funiculus was transected on one side. The operation removes descending input to all the segments caudal to the lesion. Experiments with serial transections from the caudal to rostral segment revealed that stepping activity of the limb on the lesioned side is reduced when the lesion is placed at the level between the C6 and C7 segment and then between C5 and C6. A slight reduction of activity was also observed after a lesion placed between C7 and C8. (2) Consistently, bilateral transection of the lateral funiculus at the level between C5 and C6 abolished stepping movements of both forelimbs. (3) The cervical cord was split in the parasagittal plane through the dorsal root entry. The operation removes the descending input to the segment in which the lesion is placed. The parasagittal lesions from the C1 to C6 did not abolish stepping activity, although a lesion placed between C5 and C6 could slightly affect stepping. The results, (1)-(3) suggest that the lateral funicular pathways project into the spinal segments mainly at the C6-C7 level with some rostrocaudal extension into C5 and C8.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1978

Integration in descending motor pathways controlling the forelimb in the cat. 5. Properties of and monosynaptic excitatory convergence on C3--C4 propriospinal neurones.

Recording was made in the C3--C4 segments from cell bodies of propriospinal neurones identified by their antidromic activation from more caudal segments. Monosynaptic excitatory effects from descending motor pathways and primary afferents were investigated by electrical stimulation of higher motor centres and peripheral nerves in the forelimb and neck. The cell bodies were located mainly laterally in Rexed's layer VII. Threshold mapping for single axons showed that they descend in the lateroventral part of the lateral funicle. Antidromic stimulation at different spinal cord levels showed that some neurones terminated in the forelimb segments, others in the thoracic cord or in the lumbar segments. Terminal slowing of the conduction velocity suggested axonal branching over some segments. Monosynaptic EPSPs were evoked in the neurons by stimulation of the contralateral pyramid, red nucleus and dorsal tegmentum-superior colliculus. It is concluded that corticospinal, rubrospinal and tectospinal fibres project directly to both short and long propriospinal neurones. There was marked frequency potentiation in tectospinal synapses. Convergence from two descending tracts was common and in half of the tested cells all three tracts contributed monosynaptic excitation. Experiments with collision of descending volleys and antidromic volleys from the brachial segments demonstrated that the corticospinal and rubrospinal monosynaptic projection to the propriospinal neurones is by collaterals from fibres continuing to the forelimb segments.

Action Potentials↗
PubMed1979

Comparison of dynamic properties of canal-evoked vestibulospinal reflexes of the neck and forelimb in the decerebrate cat.

The responses of neck and forelimb muscles to sinusoidal polarization of the horizontal canal nerve were compared by recording from these muscles simultaneously. Contrary to results on the vestibulocollic reflex, the central phase lag in the vestibulo-forelimb reflex increases with increasing frequencies up to 3 Hz. This demonstrates a difference in the organization of vestibular-driven pathways to neck and forelimb muscles.

Animals↗
PubMed1978

Forelimb reflexes modulated by tonic neck positions in cats.

The modulation of monosynaptic forelimb reflexes by tonic neck positions was investigated in cats with the head fixed. Lateral flexion of the body in a horizontal plane markedly facilitates reflexes of the deep radial nerve (DR) in the ipsilateral forelimb, while the antagonistic ulnar nerve (ULN) reflexes are strongly inhibited. Opposite effects are seen after contralaternal body movement. Dorsiflexion of the body clearly increases DR-reflexes and exerts a reciprocal although more pronounced inhibition on ULN reflexes. Opposite effects appear after ventriflexion. The reflex modulation starts with head-body displacements of approximately 5 degrees and increases with increasing angles. Furthermore reflex modulation does not depend on the intact cerebrum and cerebellum. The comparison of forelimb and hindlimb reflexes shows a decrease of the neck influences along the spinal cord.

Animals↗
PubMed1994

Unlike haloperidol, clozapine slows and dampens rats' forelimb force oscillations and decreases force output in a press-while-licking behavioral task.

In order to detect putative differences in the behavioral effects of clozapine and haloperidol, rats were trained to use a single forelimb to exert continuous pressure on a force-sensing operandum. Behavior was maintained by presenting a water-filled dipper for consumption only as long as the force remained above a specified level (the water fountain task). Effects of clozapine (2.0, 4.0, 8.0 mg/kg) and haloperidol (0.02, 0.04, 0.08, 0.12 mg/kg) on the forelimb force oscillations manifested during the operandum pressing episodes were analyzed with power spectral analysis and other quantitative methods. All rats exhibited force oscillations with a fundamental frequency near 7 Hz. Clozapine shifted the frequency to lower values (i.e., oscillation slowing), while haloperidol shifted oscilations to slightly higher frequencies. Moreover, clozapine reduced power in the region of the spectrum above 5 Hz. In contrast, haloperidol tended to increase power in these regions. Time domain analyses of the force-time waveforms indicated that haloperidol increased force emission during the hold phase of the forelimb response, and clozapine decreased this measure. The results are congruent with the high extrapyramidal side effects of haloperidol and the lack of such effects of clozapine in the clinic. In addition, clozapine may have antitremor effects in rats as it does in humans.

Animals↗
PubMed1997

Similarities and differences between the subchronic and withdrawal effects of clozapine and olanzapine on forelimb force steadiness.

The purpose of this study was to compare the subchronic, low-dose effects of clozapine with those of olanzapine in a learned behavioral task previously shown to distinguish between clozapine and haloperidol with acute and subchronic treatment regimes. Rats were trained to use a single forelimb to press a force-recording operandum and simultaneously to lick water from a dipper that remained available while forelimb force exceeded a modest lower limit. Analysis of the resulting forcetime recordings provided measures of task engagement (time on task-analogous to response rate), lick rhythm, tremor, ballistic (maximum force) and tonic (hold force) forelimb force measures, as well as the durations of the individual responses. In a between-groups dosing design, five separate groups of rats received vehicle, clozapine 1.0 or 5.0 mg/kg, olanzapine 0.5 or 1.0 mg/kg daily for 27 days. A 7-day withdrawal period followed. On days 22 and 26 of antipsychotic drug treatment, all rats additionally received 0.3 mg/kg trihexyphenidyl or 1.0 mg/kg quipazine, respectively. The effects of olanzapine and clozapine were similar in that both drugs reduced time on task, increased response duration, and slowed lick rhythm. The two drugs differed in that clozapine reduced the force and tremor measures but olanzapine did not. Both tolerance and withdrawal effects, as reflected by the tremor measure, were observed for clozapine but not for olanzapine. Trihexyphenidyl further increased the duration of responses already lengthened by clozapine; in contrast, trihexyphenidyl decreased the duration lengthening effect of olanzapine. Taken together, the results indicated that olanzapine did not have the antitremor and hypotonic effects displayed by clozapine, and olanzapine did not induce tolerance and withdrawal phenomena as clozapine did.

Animals↗
PubMed1999

Morphogenesis of the primary arterial trunks of the forelimb in the rat embryos: the trunks originate from the lateral surface of the dorsal aorta independently of the intersegmental arteries.

It has been believed that the primary arterial trunk of the mammalian forelimb is derived from the 7th intersegmental artery. Here we examined the early morphogenesis of the arteries and nerves in the forelimb region by adopting a method that combined intravascular dye-injection with nerve staining to whole mounted rat embryos. The study was carried out on greater numbers of specimens at smaller intervals of embryonic stages and from earlier stages than those in previous reports. We report that: (1) The multiple primary arterial trunks in the forelimb region (primary subclavians) originate directly from the lateral surface of the dorsal aorta independently of the intersegmental arteries, previous to the formation of limb buds. (2) The tips of the 8th (and the 9th) primary subclavians that originate from the aorta near the origin of the 8th (or the 9th) intersegmental artery bend cranially and/or caudally. With the formation of limb bud, they extend to form the longitudinal trunks in the presumptive axillary region. The primary arteries in the free arm region branch off from this longitudinal trunk, and one of them develops into the axial artery. (3) The origins of the primary subclavians shift their positions on the surface of the dorsal aorta and approach the origins of the neighboring intersegmental arteries to join them, and then replace the latter. Consequently, the primary subclavians appear to be "the lateral branches of the in tersegmental arteries." (4) The 8th primary subclavian is dominant at first, but is replaced by the 7th primary subclavian, which develops into the definitive subclavian artery. (5) With the brachial nerve plexus formation, the axillary arterial plexus derived from the longitudinal trunk develops to form two stems of the axillary artery.

Animals↗
PubMed1981

Measurement of fetal forelimb movements in the lamb in utero.

Forelimb movements in the unanesthetized fetal lamb in utero were measured by means of transit-time ultrasound in conjunction with triceps and biceps electromyographic activity. The relationships between forelimb movements and electrocortical activity, hypoxia, and spontaneous labor were studied. There was no evidence of diurnal variation. The amount of time spent moving in low-voltage electrocortical activity with rapid eye movements was significantly less than in other electrocortical states. During acute hypoxia, forelimb movements were much reduced. In active labor near term, the fetal electrocorticogram continued to cycle between high- and low-voltage activity, and the number of movements was reduced; movements were present only during uterine contractions, provided that the fetus was not in low-voltage electrocortical activity with rapid eye movements.

Animals↗
PubMed1975

Movements of the forelimbs of the cat during stepping on a treadmill.

In normal cats stepping on a treadmill an analysis has been made of movements of the scapula, shoulder, elbow, wrist and digits. The scapula is capable of making large and complicated movements over the rib cage. In locomotion they may be resolved into a cyclical, similunar movement of the glenoid cavity in the parasagittal plane of the cat's body. The movements of the scapula are rather constant over a wide range of velocities. They most resemble those of the hip which also shows a delay in the onset of extension and no yield phase. It is suggested that movements of the scapula have a high priority in the execution of locomotion in the forelimbs. The movements at the shoulder tend to parallel those of the elbow. The terms of palmar flexion and dorsiflexion are retained for the movements at the wrist and digits. The rapid phase of palmar flexion corresponds with the flexion phase at the elbow, and the phase of dorsiflexion with the first extension phase at the elbow. Palmar flexion during the second and third extension phases of the more proximal joints would appear to be initiated by contact of the foot with the ground. The sequences of movement at the wrist and digits allow a comparison of the roles of flexor and extensor muscles of the forearm during locomotion and the flexion reflex, which is compatible with the functional and anatomical organization of cervicothoracic segments. With exception of extension at the scapula the movements of the elbow provide an index of the onsets of flexion and extension at the other joints of the forelimb. Modifications are suggested for the Phillippson step cycle of both forelimbs and hindlimbs to include the delayed onset of extension at the scapula and hip and the particular movements of the wrist, digits and toes.

Animals↗
PubMed1996

Unilateral lesions of the forelimb area of rat motor cortex: lack of evidence for use-dependent neural growth in the undamaged hemisphere.

Unilateral lesions of the forelimb area of the motor cortex have been reported to produce enhanced dendritic outgrowth in the undamaged hemisphere in response to the behavioral asymmetry produced by the lesions (e.g. Jones, T.A. and Schallert, T., Use-dependent growth of pyramidal neurons after neocortical damage, J. Neurosci, 14 (1994) 2140-2152). We attempted to replicate this result and to determine if there were sex differences in cortical plasticity using the Jones and Schallert model. Animals were given either unilateral aspiration or electrolytic lesions of the forelimb area of the motor cortex or a sham operation. Use of the forelimb ipsilateral to the lesion for postural support was assessed pre- and postsurgery. Eighteen days after surgery the animals were sacrificed. and the brains processed for Golgi-Cox staining or a series of other stains for acetylcholine, astrocytes (glial fibrillary acidic protein), and microglia (OX-42). Although the lesions produced significant behavioral asymmetry and enhanced glial response on the lesioned side, there was little evidence for use-dependent neural growth in the undamaged hemisphere in either sex.

Acetylcholine↗
PubMed1992

The location and distribution of neural crest-derived Schwann cells in developing peripheral nerves in the chick forelimb.

The location and distribution of neural crest-derived Schwann cells during development of the peripheral nerves of chick forelimbs were examined using chick-quail chimeras. Neural crest cells were labeled by transplantation of the dorsal part of the neural tube from a quail donor to a chick host at levels of the neural tube destined to give rise to brachial innervation. The ventral roots, spinal nerves, and peripheral nerves innervating the chick forelimb were examined for the presence of quail-derived neural crest cells at several stages of embryonic development. These quail cells are likely to be Schwann cells or their precursors. Quail-derived Schwann cells were present in ventral roots and spinal nerves, and were distributed along previously described neural crest migratory pathways or along the peripheral nerve fibers at all stages of development examined. During early stages of wing innervation, quail-derived Schwann cells were not evenly distributed, but were concentrated in the ventral root and at the brachial plexus. The density of neural crest-derived Schwann cells decreased distal to the plexus, and no Schwann cells were ever seen in advance of the growing nerve front. When the characteristic peripheral nerve branching pattern was first formed, Schwann cells were clustered where muscle nerves diverged from common nerve trunks. In still older embryos, neural crest-derived Schwann cells were evenly distributed along the length of the peripheral nerves from the ventral root to the distal nerve terminations within the musculature of the forelimb. These observations indicate that Schwann cells accompany axons into the developing limb, but they do not appear to lead or direct axons to their targets. The transient clustering of neural crest-derived Schwann cells in the ventral root and at places where axon trajectories diverge from one another may reflect a response to some environmental feature within these regions.

Animals↗
PubMed1986

Elevations of cathepsin B and cathepsin L activities in forelimb and hind limb muscles of genetically dystrophic mice.

The combined activities of cathepsin B and cathepsin L were studied in the forelimb and hind limb muscles of dystrophic mice. The activities of these proteases in the forelimb and hind limb muscles of young and adult dystrophic mice were significantly higher than those in normal mice. However, clinical involvement of dystrophy appeared in the hind limbs but not in the forelimbs. We therefore suggest that the increase in protease activity begins at a very early age and that the clinical involvement is not linked with the increase in cathepsin B and L.

Animals↗
PubMed1995

Sympathetic and afferent neurones projecting into forelimb and trunk nerves and the anatomical organization of the thoracic sympathetic outflow of the rat.

The anatomy of the cervicothoracic sympathetic nerves was studied in the rat. Details of the arrangements of white and grey rami communicantes and superior cervical, middle cervical and stellate ganglia are given. Dorsal root and sympathetic ganglion neurones projecting to skin and muscle of the forelimb and trunk were labelled retrogradely with horseradish peroxidase (HRP) in order to study their number, segmental distribution and location. HRP was applied to forelimb nerves supplying skeletal muscles (Ramus profundus of radial nerve, RP) or hairy skin (N. cutaneus brachii lateralis superior of axillary nerve, CB), to mixed nerves (median nerve, ME; ulnar nerve, UL; radial nerve, RA) and to segmental thoracic nerves supplying hairy skin of the back (dorsal cutaneous nerve, CD) and to mixed internal intercostal nerves (IC). All sensory and sympathetic neurones were located ipsilaterally. In the forelimb nerves sensory somata were commonly restricted to two or three adjacent dorsal root ganglia (usually C6-7 for CB; C7-8 for ME; C7-Th1 for RA and RP; C8-Th1 for UL). Nearly all of the sympathetic somata were located in the middle cervical and stellate ganglia (fusion of C6-Th3). Some 0-0.4% lay in Th4 and Th5, none in the superior cervical ganglia. In the trunk nerves sensory somata were strictly segmentally organized. Sympathetic somata were distributed more widely over 4-5 segments with 50-55% in the segmental ganglion and up to 41% in the next caudal segment. From the data, it is estimated that 400 sympathetic (28%) and 1050 afferent neurones project into CB, 1660 (29%) and 4050 into RA, 540 (42%) and 760 into RP, 1010 (22%) and 3670 into ME, 880 (22%) and 3040 into UL, 350 (25%) and 1040 into IC and 500 (27%) and 1370 into CD.

Animals↗
PubMed1995

The dorsomedial frontal cortex: eye and forelimb fields.

This review yields three conclusions: first, the eye field as described using unit recording and electrical stimulation on behaving monkeys trained to fixate visual targets is much larger than the 4 mm2 area originally described. Second, the eye field and forelimb field share a similar neural space within the dorsomedial frontal cortex (DMFC); thus the electrophysiogical studies that have been conducted on visually guided and sensory-triggered forelimb movements must be re-evaluated, since none of these studies controlled eye movement and eye position independently. Third, a topographic map representing eye position in orbit has been discovered in the DMFC; it is proposed that this topographic map records the order of positions of the eyes and forelimbs during the acquisition of visually guided movement sequences.

Animals↗
PubMed1979

Neuronal activity in the cortical supplementary motor area related with distal and proximal forelimb movements.

Monkeys were trained to perform two different motor acts, one involving muscle activity in distal forelimb muscles and the other in proximal forelimb and shoulder girdle muscles. After confirming spatial and temporal dissociation of muscle activity in the two motor acts, single unit activity in the supplementary motor area (SMA) was recorded. SMA neurons related with the distal and proximal forelimb movements were found to be arranged rostrocaudally with a considerable overlap. In the overlapping region, neurons related with the distal movement were located more deeply.

Animals↗