Transneuronal and peripheral mechanisms for the induction of motor neuron sprouting

Abstract

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. ) 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 axotomy. 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.

Recovery of tail-elicited siphon-withdrawal reflex following unilateral axonal injury is associated with ipsi- and contralateral changes in gene expression in Aplysia californica

“…For example, in cat hemisected spinal cord, recovery of reflexes and locomotion involves sprouting in contralateral pathways (Helgren and Goldberger, 1993). Sprouting of undamaged pathways following injury has also been reported in frog motor neurons and rat dentate gyms following unilateral injury (Steward et al, 1976;Rotshenker, 1982). The injury-induced signal(s) that alters gene expression and causes sprouting are not known at present.…”

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

“…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(Rotshenker, , 1982) the underlying mechanism may be the transneuronal induction of sprouting and synapse formation. …”

Incoming synapses and size of small granule‐containing cells in a rat sympathetic ganglion after post‐ganglionic axotomy.

“…The possibility that the contralateral changes were induced by a retrograde trophic influence on the preganglionic neurones is raised by the experiments of Rotshenker and others (Rotshenker & McMahan, 1976;Rotshenker, 1979Rotshenker, , 1982Reichert & Rotshenker, 1979) on the motor innervation of skeletal muscle. These authors similarly observed contralateral effects: they found nerve sprouting from undamaged motor axons in the contralateral muscle after unilateral denervation of the frog cutaneus pectoris muscle; this sprouting occurred earlier, the closer the lesion was placed to the spinal cord, and could also follow the application of colchicine to the nerve.…”

“…Such a consequence might be analogous to the detachment of preganglionic synapses from injured principal neurones, if the latter is to be attributed to the loss of retrogradely transported factors from their peripheral target tissues. The small granule-containing cells themselves should escape direct injury after post-ganglionic axotomy, since they exhibit only short processes which are not observed to extend into the post-ganglionic nerve trunks, and there is, moreover, direct evidence that cutting these trunks is not followed by any loss of these cells (Soinila & Eriink6, 1980, 1982; but the dissociation of their outgoing synapses to the principal neurones might deprive them of some target-derived factor essential for the maintenance of their own preganglionic synaptic input. A quantitative analysis of synapses has been made, including the use of stereology; data on the innervation of the small granule-containing cells in normal ganglia, from Case & Matthews (1985), have been used as a basis for comparison.…”