The Journal of Neuroscience, October 15, 1999, 19(20):8931-8944
Neonatal Partial Denervation Results in Nodal But Not Terminal
Sprouting and a Decrease in Efficacy of Remaining Neuromuscular
Junctions in Rat Soleus Muscle
Jane L.
Lubischer and
Wesley J.
Thompson
Section of Neurobiology, School of Biological Sciences, Institute
for Neuroscience and Institute for Cellular and Molecular Biology,
University of Texas, Austin, Texas 78712
Mature motoneurons respond to partial denervation of their target
muscle by sprouting to reinnervate denervated fibers, thus maintaining
muscle strength in the face of motoneuronal loss caused by injury or
disease. Neonatal motoneurons, however, do not expand to innervate more
muscle fibers. The present work seeks to understand this developmental
change in motoneuron response to partial denervation. It has been
suggested that neonatal motor units cannot increase in size because
they are already at their maximum size (approximately five times larger
than in adulthood). We ruled out this explanation by showing that after
partial denervation on postnatal day 14 (P14), when motor units have
decreased to their adult size, motoneurons still did not sprout to
reinnervate as many fibers as in adulthood. Instead, we found evidence
supporting an alternative explanation involving terminal Schwann cells.
After partial denervation of neonatal (but not adult) muscles, terminal
Schwann cells at denervated endplates undergo apoptosis. We found that
terminal (but not nodal) sprouting was absent in partially denervated
neonatal muscles. This finding suggests that terminal Schwann cells,
previously reported to guide terminal sprouts to denervated endplates
in adult muscles, are necessary for the formation and growth of
terminal sprouts. Moreover, partial denervation on P14 severely
weakened the remaining, uninjured synapses, suggesting that neonatal
motoneurons may withdraw terminals after the denervation of nearby
fibers. These findings have implications for the interpretation of
previous studies on synapse elimination and offer insight into the
failure of young motor units to expand after partial denervation.
Key words:
Schwann cells; synapse elimination; NMJ; synaptic
strength; development; motoneuron; curare
Copyright © 1999 Society for Neuroscience 0270-6474/99/19208931-14$05.00/0