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S Rotshenker

Publications and source records attributed to S Rotshenker.

At least 37 records · Page 2Linked to original sources

The transneuronal induction of sprouting and synapse formation in intact mouse muscles.

The pattern of innervation to intact peroneal and extensor digitorum longus muscles of normal and experimental young adult mice was studied by light microscopy after staining neuromuscular junctions by a combined silver-cholinesterase stain. Spontaneous sprouting and synapse formation occur in intact muscles of normal mice. In about 7% of the junctions, sprouts contribute to the innervation of muscle fibres already innervated by their parent axons. Axotomy of the sciatic nerve in one hind limb is followed by an average 3-fold increase over normal in the incidence of sprouting and synapse formation in the intact muscles of the opposite hind limb. The time to onset of sprouting and synapse formation becomes shorter as the site of the contralateral axotomy is placed closer to the spinal cord. A significant increase over normal in the incidence of sprouting is first observed 5 days after a proximal sciatic nerve cut and only 12 days after a distal sciatic nerve cut. The timing of sprouting is independent of the difference in the number of axons that are involved in the contralateral axotomies at different sites. These findings suggest that, in the intact muscles of normal mice, sprouting and synapse formation is an ongoing process which can be enhanced by contralateral axotomy. As in frogs (Rotshenker, 1979, 1982) the underlying mechanism may be the transneuronal induction of sprouting and synapse formation.

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Sprouting and synapse formation produced by Carbocaine.

Injury to one cutaneous pectoris nerve of the frog induces sprouting of and synapse formation by the contralateral homologous intact nerve. It was previously suggested that axotomy initiates a signal for growth in the cell bodies of the injured motor neurons and that this signal is transferred transneuronally across the spinal cord to intact motor neurons (e.g., Rotshenker, S. (1982) J. Neurosci. 2: 1359-1368). The present study was designed to test the hypothesis that axotomy initiated the signal for growth by depriving neuronal somata of a trophic substance derived from the target muscle. The superficial layer of muscle fibers comprising one cutaneous pectoris muscle, the source of the hypothetical trophic substance, was removed by means of local application of the myotoxic local anesthetic Carbocaine. An increased supernumerary pattern of innervation developed in drug-treated muscles first and in contralateral intact muscles thereafter. These results raise the possibility that target muscle fibers play a role as regulators of a signal for growth in the cell bodies of their innervating motor neurons.

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Recycling of synaptic vesicles in motor nerve endings separated from their target muscle fibers.

The application of the myotoxic local anesthetic Carbocaine to the cutaneous-pectoris muscle of the frog produced muscle fiber degeneration. The degenerating muscle fibers were phagocytozed by macrophages leaving behind structurally intact motor nerve endings in close apposition to the sheath of basal lamina that normally surrounds muscle fibers. These target deprived nerve terminals retained their ability to recycle synaptic vesicles in that they showed a low basal rate of spontaneous uptake of HRP that increased several fold upon nerve stimulation.

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Sprouting in intact sartorius muscles of the frog following contralateral axotomy.

The intact hind limb sartorius muscle of the frog was examined anatomically for sprouting following axotomy of the sciatic nerve that contains motor axons innervating the contralateral sartorius muscle. The incidence of sprouting in intact muscles of experimental animals increased more than 3-fold over normal. Thus, contralateral axotomy produces sprouting in intact sartorius muscles much the same as it does in cutaneous-pectoris and piriformis muscles of the frog.

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Transneuronal and peripheral mechanisms for the induction of motor neuron sprouting.

After injury to the nerve to one cutaneous pectoris muscle of the frog, the intact nerve to the contralateral muscle sprouts and forms additional synaptic connections with already innervated muscle fibers. It has been suggested (Rotshenker, S. (1979) J. Physiol. (Lond.) 292: 535-547; Rotshenker, S., and F. Reichert (1980) J. Comp. Neurol. 193: 413-422) that axotomy initiates a signal for sprouting in the injured neurons that is transferred transneuronally across the spinal cord to intact motor neurons. The present study was designed to test the hypothesis that axotomy initiates the signal for sprouting by interfering with some trophic signaling between the injured neurons and denervated muscle. Colchicine therefore was applied to the nerve to the left muscles to inhibit axonal transport on whose integrity trophic interactions depend. Consequently, supernumerary innervation developed in contralateral right intact muscles much the same as after axotom. Surprisingly, axons that were exposed to the drug also sprouted and formed synapses. Furthermore, the sprouting response of axons that were exposed to the drug also was produced in nerve fibers that were separated from their cell bodies. These results suggest two ways in which colchicine may produce sprouting and synapse formation and thereby suggest two mechanisms by which motor neurons may be induced to sprout: (a) transneuronally, by presenting growth stimuli to their cell bodies and central processes in the central nervous system and (b) by presenting growth stimuli to their peripheral extensions.

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Synapse formation in intact innervated cutaneous-pectoris muscles of the frog following denervation of the opposite muscle.

1. Denervation of one cutaneous-pectoris muscle of the frog induces the formation of new synapses in the intact innervated muscle on the opposite side. After crushing the motor nerve to the left muscle the incidence of polyneuronal innervation in the right intact muscle increased from an average normal value of 16% to an average value of 27% (Rotshenker & McMahan, 1976).2. The formation of the new synapses in the intact muscle is independent of the presence of denervated muscle fibres or degenerating axons peripheral to the site of axotomy. After removing the left cutaneous-pectoris muscle, the proportion of polyneuronally innervated muscle fibres in the right intact muscle increased to an average value of 34%.3. The number of new synapses formed in one muscle is dependent upon the type of the lesion to the motor nerve to the opposite muscle; 40% of the muscle fibres on the right side were found to be polyneuronally innervated after transecting the motor nerve on the opposite side, as compared to 27% after crushing it.4. The delay with which new synapses are formed on the unoperated side is dependent upon the distance from the spinal cord of the axotomy. New synapses were detected 4-8 weeks after cutting the opposite nerve close to the muscle. Placing the site of axotomy close to the spinal cord shortened the delay and new synapses were detected as early as 9 days after the operation.5. The stimulus for the formation of new synapses by an intact nerve is ineffective if the injured nerve on the contralateral side originates from distant segments of the spinal cord. The pattern of innervation in cutaneous-pectoris muscles was not altered following denervation of distant muscles in the hind limb.6. These results suggest that the signal for sprouting and synapse formation may arise in the damaged nerve cells, central to the site of axotomy, and then be communicated transneuronally within the spinal cord to the intact motoneurones on the opposite side.

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Quelling of spontaneous transmitter release by nerve impulses in low extracellular calcium solutions.

1. The effect of nerve stimulation on spontaneous transmitter release was studied at the frog neuromuscular synapse which was bathed in a solution containing very low extracellular calcium concentration. Conventional methods for intracellular and extracellular recording were used and the pattern of quantal liberation following the nerve stimulus was determined. 2. Stimulation of the motor nerve (at rates between 0.09 and 2Hz) caused a reduction in the frequency of the miniature e.p.p.s in comparison to the prestimulation values. 3. The mean distribution of the time of occurrence of the miniature e.p.p.s during the interstimulus period showed periodic oscillations. 4. The quelling effect of nerve stimulation on transmitter release is explained by the hypothesis that a low [Ca]o a reversed electrochemical gradient for calcium occurs and nerve stimulation causes an increased calcium conductance leading to calcium efflux which in turn temporarily reduces [Ca]i and transmitter release.

Action Potentials↗

Altered patterns of innervation in frog muscle after denervation.

The pattern of reinnervation of muscle fibres after a nerve crush was examined in the cutaneous pectoris muscle of the frog by microscopy and electrophysiology. Normally, about 16% of the muscle fibres are innervated by more than one motor neuron. Two months after reinnervation, about 50% of the fibres are polyneuronally innervated and this high incidence persists for at least seven months. The total number of neurons reinnervating the muscle, as well as the number of muscle fibres comprising the muscle, are normal. However, nerve fibres sprout branches at the site of the crush, and, therefore, the number of axons entering the muscle is greater than normal. Regenerating axons contact muscle fibres precisely at the original synaptic sites and the terminal branches from different axons that end on the same muscle fibre often run side by side occupying stretches or original postsynaptic membrane normally covered by one terminal. Our findings indicate that the amount of synaptic contact during regeneration is limited by the amount of original postsynaptic membrane and that any number of axons that reach vacant portions of original postsynaptic membrane can make synaptic contact with it. Surprisingly, control cutaneous pectoris muscles, situated contralaterally to those that were denervated, also exhibited an abnormal pattern of innervation. Although neither nerve nor muscle was disturbed by the operation, there was a higher incidence of polyneuronal innervation (27% vs 16%) than in muscles of normal animals.

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Neuromuscular synapse: stochastic properties of spontaneous release of transmitter.

The spontaneous quantal release of transmitter from the motor nerve endings is a random process which follows the Poisson theorem; the liberation of each quantum is independent of the release of previous quanta. Increase in the extracellular calcium concentration produces a statistical interdependence in the release of the spontaneously appearing packages.

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