PubMed Health⌕ Search

Biomedical subjects

P B Farel

Publications and source records attributed to P B Farel.

At least 19 recordsLinked to original sources
PubMed1992

Neuromuscular specificity following cross-stage hindlimb transplantation.

In order to determine whether spinal motoneurons can regenerate to their proper targets at stages beyond those when such specificity is typically expressed, autologous and homologous (same- and cross-stage) hindlimb transplantations were performed using bullfrog tadpoles (Rana catesbeiana). Neuromuscular specificity was assessed by applying horseradish peroxidase to the ventral thigh of the transplanted hindlimb and mapping the locations of retrogradely labeled motoneurons. Previously, we found that the hindlimb was reinnervated normally in young tadpoles whose motor nerves were transected. However, motor axons in older animals showed no evidence of target specificity when reinnervating the tadpole's own limb. In the present study, innervation was normal in young tadpoles whose hindlimb was removed and replaced in its original position. Axons of older hosts innervating hindlimbs transplanted from young tadpoles distinguished flexor from extensor limb regions, but failed to distinguish thigh from shank, demonstrating that axons in older animals can respond to at least some guidance cues. The lack of specificity along the proximal-distal axis appears to be a consequence of homologous transplantation since limbs transplanted from one young tadpole to another showed the same loss of proximal-distal specificity. One possibility is that the shank degenerates when the hindlimb is transplanted to a different host. Shank motoneurons, lacking their proper target, may then innervate the thigh. However, shank motoneurons did not innervate the thigh when motor nerve transection was combined with amputation of the hindlimb just above the presumptive knee.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Neuron addition in the postmetamorphic frog.

Neuron number among somatic motoneurons, sensory neurons, and sympathetic postganglionic neurons that innervate the hindlimb was correlated with body length in the bullfrog, Rana catesbeiana. Two to three times more dorsal root and sympathetic ganglion neurons are found in the largest than the smallest specimens. Hindlimb motoneurons show a 20% increase in number, but this increase is restricted to the caudal third of the motor pool. Within this region, 60% more motoneurons are found among the largest frogs. Cell division does not appear to be the mechanism of neuron addition. Instead, we propose that a pool of undifferentiated neurons mature to maintain functional capabilities as the animal increases in size.

Animals↗
PubMed1990

Mauthner cells maintain their lumbar projection in adult frog.

We have used retrograde labeling with horseradish peroxidase (HRP) in the bullfrog. Rana catesbeiana, to determine whether Mauthner (M) cells maintain a projection to the lumbar spinal cord in adult bullfrogs. We found that M cells persist in the adult bullfrog and maintain a projection to the lumbar spinal cord, despite the degeneration of much of their afferent input and of their motoneuronal targets in the spinal cord.

Animals↗
PubMed1989

Regenerative specificity of motor axons when reinnervation is partially suppressed.

We asked whether regenerating hindlimb motor axons would innervate inappropriate hindlimb regions if competition from appropriate innervation were prevented. The three ventral roots that innervate the hindlimb in the bullfrog (Rana catesbeiana) tadpole were transected, and the two more rostral roots were ligated to prevent regeneration. The most caudal root, which primarily supplies more distal limb musculature in unoperated tadpoles, was left free to regenerate. The specificity of regeneration was assessed by retrogradely labeling spinal motoneurons with HRP placed in the ventral thigh, a region that receives most of its innervation from the ligated roots. Despite the lack of competition from appropriate innervation, the regenerating root did not provide substantial innervation to proximal limb musculature. The same result was obtained in tadpoles operated upon at stages when regeneration of motor axons is specific and in tadpoles at stages when regenerating motor axons do not reinnervate their appropriate targets (Farel and Bemelmans, 1986), although the mechanisms in each case are likely different.

Animals↗
PubMed1989

Naturally occurring cell death and differentiation of developing spinal motoneurons following axotomy.

The purpose of this study was to examine the effects of axon transection on the development and differentiation of spinal motoneurons in the bullfrog (Rana catesbeiana) tadpole. The 3 ventral roots (VRs) that innervate the hindlimb were transected, and the animals were killed 6-7 weeks later (reinnervation took place within 3 weeks). At early stages of development, axotomy resulted in an increase in the number of spinal motoneurons on the operated side. By histological criteria, these motoneurons appeared more differentiated than those in normal tadpoles. Axotomy was effective in increasing motoneuron number only during the period of naturally occurring cell death. Similar effects were seen when the transected VRs were ligated to prevent regeneration. Hindlimb amputation without VR transection had no effect on motoneuron number or differentiation. Thus, target removal is neither a necessary nor a sufficient condition for hyperplasia of the lateral motor column. An extreme loss of spinal motoneurons was seen if the operated tadpole entered into metamorphic climax during the 6-7-week postoperative survival period. Motoneuron loss occurred although the injured motoneurons had reconnected to the hindlimb. In contrast, tadpoles allowed to survive up to 6 months showed no loss of motoneurons if they did not enter metamorphic climax. From these data, it appears axon transection in developing spinal motoneurons exerts its effects on motoneuron number and differentiation by altering the metabolic state of the motoneuron (axon reaction) rather than by depriving it of contact with its target.

Amputation, Surgical↗
PubMed1988

Guidance of regenerating motor axons in larval and juvenile bullfrogs.

The segmental distribution of regenerating bullfrog motor axons was mapped in advanced tadpoles and juvenile frogs by stimulating selected muscle nerves and recording from the distal ends of the 3 lumbar ventral roots (VRs) that innervate the hindlimb. When motoneurons were axotomized by VR transection, they reestablished their original innervation fields, rarely, if ever, growing beyond the territory normally supplied by their spinal segment. However, when motoneurons were axotomized in the spinal nerves at the level of the hindlimb plexus, some of them regenerated into limb nerves that lay outside the axons' normal segmental boundaries, and many regenerated into the medial femoral cutaneous nerve, a pathway normally limited to sensory axons. These observations suggest that the ultimate destinations of regenerating axons are largely determined by structures the axons encounter as they penetrate the distal nerve stumps. Thus, axons regenerating from a severed VR grow into that root's own distal stump and reinnervate the hindlimb in a manner that is segmentally appropriate; axons transected near the plexus have access to the pathways of sensory, as well as motor, axons in all 3 lumbar segments, and establish innervation fields that are inappropriate for their segment of origin and their motor function.

Animals↗
PubMed1987

Motoneuron number in the lumbar lateral motor column of larval and adult bullfrogs.

Motoneuron number in the lumbar lateral motor column of the bullfrog, Rana catesbeiana, was investigated through the course of premetamorphic development and in postmetamorphic frogs. Motoneurons were distinguished on the basis of histological characteristics into two classes, type L (less differentiated) and type M (more differentiated). The number of type L motoneurons on each side showed a precipitous decline between stages V and VI (6,300 to 2,500) and a slower rate of loss until stage XI (to 550). Type M motoneurons increased in number between stages V and VII (560 to 2,775) and declined precipitously between stages VII and VIII to a value similar to that of juvenile frogs (1,100). These changes in motoneuron number do not correspond to the formation of myotubes or to the appearance of contractile properties in hindlimb muscles. The development of myotubes in the hindlimb occurs only after total motoneuron number has declined by 35%. Similarly, hindlimb muscle contraction develops after the early decline in type L motoneuron number and is restricted to proximal thigh at the peak of type M motoneuron number. In postmetamorphic frogs, a weak (r = 0.44) but statistically significant correlation was found between type M motoneuron number and body length. In the largest frogs (greater than 15 cm body length), 1262 +/- 157 (mean +/- s.d.) motoneurons were present, whereas the smallest frogs (less than 5 cm body length) had 1099 +/- 98 motoneurons. These results are not consistent with previous findings that the variance of motoneuron number among small frogs is greater than that among larger frogs. The present results are thus inconsistent with explanations of size-related differences in motoneuron number that are based on selection of small frogs with greater number of motoneurons for survival. The increase in motoneuron number may be due to a slow addition of newly born motoneurons to the LMC or to the differentiation of existing motoneurons. The latter possibility is supported by the finding that the number of presumptive type L profiles is less in larger frogs.

Animals↗
PubMed1986

Restoration of neuromuscular specificity following ventral rhizotomy in the bullfrog tadpole, Rana catesbeiana.

The specificity of hindlimb reinnervation following transection of lumbar ventral roots was investigated in adult and larval bullfrogs (Rana catesbeiana). Five to 6 weeks following ventral rhizotomy, the retrogradely transported marker horseradish peroxidase (HRP) was applied to circumscribed regions of the hindlimb. The location of labeled motoneuron somata within the lumbar lateral motor column was compared with that obtained in unoperated tadpoles. Reinnervation of the hindlimb was largely specific in tadpoles operated during the first third of larval life. However, localization was largely lost in older tadpoles and adult frogs. Repeated applications of 3H-thymidine combined with retrograde labeling with HRP failed to provide evidence that newly born motoneurons contribute to reinnervation of the hindlimb. Hindlimb reinnervation thus appears to result from regeneration of transected motor axons. In contrast to the lack of neuromuscular specificity seen in older animals after transection of ventral roots, motoneuron axons disconnected from their targets by crush injury regenerate to the appropriate limb regions.

Age Factors↗
PubMed1986

Specificity of neuromuscular connections during early development and following regeneration of motor axons in the bullfrog.

The specificity of neuromuscular connectivity was examined in unoperated bullfrog (Rana catesbeiana) tadpoles and in tadpoles that had undergone transection of the three ventral roots that normally innervate the hindlimb. The specificity of motoneuron projections was assessed by applying small amounts of horseradish peroxidase to circumcribed hindlimb regions and mapping the locations of retrogradely labeled motoneurons within the lumbar lateral motor column (LMC). In unoperated tadpoles, the locations of retrogradely labeled motoneurons in the LMC were as circumscribed at early stages of development as in tadpoles examined after motoneuron number in the LMC had stabilized. Six to eight weeks after ventral root transection in young tadpoles, localization of retrogradely labeled motoneurons was almost as circumscribed as found in unoperated tadpoles. However, localization following regeneration became less precise in more advanced tadpoles. If the ventral roots of adult frogs were crushed rather than transected, motor axon regeneration was considerably more precise, confirming previous reports (Westerfield and Powell, 1983). The implications of these results for hypotheses of neuromuscular specificity are discussed.

Animals↗
PubMed1985

Specificity of motoneuron projection patterns during development of the bullfrog tadpole (Rana catesbeiana).

The pattern of connectivity between motoneurons of the lumbar lateral motor column (LMC) and hindlimb regions was examined in bullfrog tadpoles (Rana catesbeiana) over the course of larval development. The purpose of this study was to determine if a period of relatively imprecise connectivity, such has been found in the toad Xenopus laevis (Lamb, '76), could be identified. Patterns of connectivity were assessed by placing small amounts of the retrogradely transported enzyme horseradish peroxidase (HRP) into discrete hindlimb regions and mapping the locations of labeled motoneuron somata along the transverse and longitudinal axes of the LMC. The distribution of labeled motoneurons was as circumscribed in the youngest animals studied (st. IV of Taylor and Kollros, '46), before mesenchymal condensation into distinct myotubes, as in metamorphic or adult animals. This finding that the pattern of neuromuscular connectivity is as precise early in development as in mature animals is consistent with previous studies of chick hindlimb (Landmesser, '78). The relevance of these results to the hypothesis that naturally occurring cell death plays a substantial part in molding the mature pattern of neuromuscular connectivity (Lamb, '77) is discussed.

Animals↗
PubMed1985

Pharmacological activation of locomotor patterns in larval and adult frog spinal cords.

The effects of amino acids, catecholamines, and their agonists shown to elicit locomotor activity in several vertebrate species were examined in spinal animals and isolated nervous systems of developing tadpoles (Rana catesbiana) and adult frogs (R. catesbiana and pipiens). Elicited activity was correlated in spinal animals by video and electromyographic analysis, and in in vitro spinal cords by recordings of tail and hindlimb motor activity. Of the agents tested, only N-methyl-DL-aspartate (NMA), an amino acid agonist, was effective in eliciting motor activity in spinal animals. In isolated nervous systems, both NMA and D-glutamate added to the bath activated locomotor activity. NMA injected i.p. into tadpoles with high spinal cord transections elicited coordinated swimming motor activity in axial and hindlimb muscles that was roughly typical for the stage of development of the animal. In late stage tadpoles (st. XX), NMA also elicited wiping and alternating or synchronous (i.e. kicking or jumping) hindlimb movements. Addition of NMA or glutamate to a bath containing an in vitro tadpole spinal cord preparation elicited ventral root motor activity characteristic of swimming, but without a rostrocaudal phase lag. Rhythmic activity thought to underlie stepping and kicking was seen in lateral ventral rootlets innervating the hindlimbs. In adult frogs with high spinal cord transections, injection of NMA elicited a general sequence of spontaneous hindlimb motor functions: reflex wiping, stepping, and kicking or jumping. Isolated frog spinal cords were not responsive to bath applied NMA, under the present conditions. The activation by amino acids or their agonists of different motor functions in both larval and adult frogs, as well as in higher and lower vertebrates, suggests a general significance of amino acid-activated receptors in the neural networks controlling locomotor function.

2-Aminoadipic Acid↗
PubMed1985

Development of locomotor mechanisms in the frog.

Tadpoles swim by undulations of the body and tail, whereas frogs locomote by alternate (stepping) and synchronous (frog-kick) movements of the hindlimbs. The development of interlimb coordination was studied by recording the activity of hindlimb motoneurons from the left and right ninth ventral roots of the isolated central nervous system (CNS). Results showed that mechanisms responsible for interlimb coordination of stepping are functional when the hindlimb is still composed of undifferentiated mesenchyme and before the lateral motor column has stabilized (stage III). The early appearance of coordinated activation of hindlimb motoneurons suggests that innervation of appropriate target muscles is not a prerequisite for normal development of circuits that mediate interlimb coordination of stepping. Synchronous activation of left and right hindlimb motoneurons (fictive frog kicks) appeared later in development (stage XIV). Throughout larval development 1:1 frequency coupling between both alternating and synchronous bursts of hindlimb motoneurons and bursts of primary motoneurons (those innervating axial muscles) was found. Recordings of peripheral nerve activity showed that motoneurons innervating antagonistic muscles of the thigh burst in antiphase. This intralimb coordination was present at stage X, a foot paddle stage that was the earliest stage in which the peripheral nerves were successfully dissected. That the neural activity of the isolated nervous system described above indeed underlies coordinated locomotor movements of the hindlimbs was shown by single-frame videotape analysis of hindlimb movements produced by the otherwise isolated CNS. The stepping movements displayed by those preparations were consistent with patterns of electrophysiological burst activity recorded from the ventral roots and peripheral nerves. The ontogenetic sequence in which the different patterns of electrophysiological activity emerged is the same as that of the corresponding behaviors in the intact tadpole. Although there were developmental changes in the reliability with which coordinated activity in the ventral roots and peripheral nerves was observed, each mode of coordination remained qualitatively unchanged from its earliest appearance through metamorphosis. These results show that mechanisms underlying locomotor coordination of the hindlimbs develop very early in larval ontogeny of the frog and can function when isolated from the periphery.

Afferent Pathways↗
PubMed1979

Initiation and time course of mitosis of non-neuronal cells after spinal motoneuron axotomy.

The mitotic response of non-neuronal cells following motor axon transection was measured after in vitro incorporation of [3H]thymidine in frog spinal cord. This predominantly ipsilateral response occurs more rapidly and is of greater magnitude when motor axons are unilaterally transected at the ventral root than after sciatic nerve transection. No increase in incorporation occurred when regenerating fibers were transected a second time before reinnervation, but an increase was observed when the second operation was performed after the formation of functional neuromuscular connections had taken place. Autoradiographic studies after dorsal or ventral root transection showed that the distribution of labeled cells approximated the anatomical extent of the injured cellular elements within the spinal cord. These data are discussed in relation to the characteristics of the dividing cells and the nature of the events eliciting mitosis.

Animals↗
PubMed1978

Reflex activity of regenerating frog spinal motoneurons.

The reflex activity of frog spinal motoneurons whose axons had been sectioned 7 days to 10 months previously was examined. Before the severed axons reinnervated muscle, reflex latency was prolonged, and reflex amplitude was depressed. Examination of input-output relations revealed the presence of a subset of axotomized motoneurons having supranormal excitability. This subset was not present in normal preparations or in preparations tested after reinnervation took place. Following reinnervation of muscle, reflex latency returned to preoperative levels, while amplitude recovery was typically more variable. Decreased conduction velocity of the severed ventral root fibers accounted for the alterations in reflex latency. These and other data form the basis for concluding that motoneurons, even within a particular preparation, show a wide range of responses to section of their axons and will provide a framework for interpretation of more selective intracellular experiments.

Animals↗
PubMed1976

Habituation of a monosynaptic response in frog spinal cord: evidence for a presynaptic mechanism.

1. Using the isolated spinal cord of bullfrogs (Rana catesbeiana), intracellular correlates of habituation-like depression of the monosynaptic response elicited in motoneurons by lateral column (LC) stimulation were investigated. The following properties of the motoneuron were compared before and after response depression produced by stimulation of the LC at 0.5/s: resting membrane potential, membrane conductance, critical firing level, and rheobasic current. No alteration was found in any of these parameters. 2. To determine whether transmitter release mechanisms were changing over trials, the LC was stimulated with pairs of stimuli separated by 6 ms presented at 0.5/s. While the amplitude of the first EPSP declined (74% of initial value), the amplitude of the second EPSP increased (111% of initial value). Facilitation ratios thus increased. 3. The following conclusions can thus be drawn: 1) habituation involves a process intrinsic to the LC-motoneuron synapse; 2) habituation is not totally mediated by receptor desensitization; 3) habituation is not mediated by a mechanism extrinsic to the LC-motoneuron synapse that depolarizes terminal endings, e.g., presynaptic inhibition or accumulation of extracellular potassium; 4) habituation is not produced by transmitter depletion. Any of these possibilities has as a necessary consequence that facilitiation ratios remain unchanged. 4. Possible mechanisms that could mediate habituation are: 1) alterations in mobilization and/or release of transmitter; 2) decreased probability of invasion of terminal branches of the presynaptic fiber by the action potential.

Animals↗