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Abstract
Activity blockade with neuromuscular antagonists during the period of motoneuronal cell death rescues motoneurons normally destined to die. This rescue has been proposed to be mediated by an increase in the sites of uptake of target-derived trophic factor resulting from an increase in intramuscular nerve branching that follows, and is presumed to be a consequence of, activity blockade. Neuromuscular blockers also affect motoneuronal activation patterns normally functioning during the period of cell death. This raises the possibility that these effects may not require the blockade of neuromuscular activity, however, the role of activity per se has not been separately evaluated.
The pattern of intramuscular nerve branching was evaluated after chronic treatments with different doses of d-TC that result in different degrees of activity blockade. This study shows that intramuscular nerve branching is correlated with the degree of muscle electrical activity. However, addition of CGRP to d-TC treated embryos, which does not modify the d-TC block of embryonic motility, resulted in a reduction of intramuscular branch formation which was more pronounced in fast than in slow muscle. Therefore intramuscular branching can be regulated not only by an activity dependent mechanism but can also be modified through a second mechanism that does not require muscle activation.
Changes in the pattern of intramuscular nerve branching have been shown to be modified by alterations of the level of polisialylation of nerve NCAM. The changes in intramuscular nerve branching described in this study were not associated with changes in PSA-NCAM in nerve.
This provides an alternative model in which to study the regulation of cell death by intramuscular nerve branching whereby different degrees of neuromuscular contact can be achieved without modification of the activity level (by addition of CGRP) or nerve PSA-NCAM changes associated with them.