REDUCTION OF INTRAMUSCULAR NERVE BRANCHING AND SYNAPTOGENESIS IS CORRELATED WITH DECREASED MOTONEURON SURVIVAL

Blockade of neuromuscular activity during the period of naturally occu rring cell death increases intramuscular nerve branching, synaptogenes is, and survival of embryonic chicken motoneurons. These results sugge sted that the enhanced motoneuron survival observed might result not f rom increased production of a trophic factor by the target, as often s uggested, but rather from the enhanced ability of motoneurons to take up this factor via additional branches and/ or synapses. Since removal of polysialic acid (PSA) by PSA-specific endoneuraminidase (endo N) d uring the period of nerve ingrowth and motoneuron cell death had been shown to reduce intramuscular nerve branching by altering adhesive int eractions between axons and myotubes, we wished to determine, first, i f this resulted in a reduction of synapse formation, and second, if th is was correlated with decreased motoneuron survival. When PSA was rem oved from embryonic day 6 (E6) to Eg by injecting endo N into the limb , the number of synapses in the posterior iliotibialis muscle was grea tly reduced both at E6.5, the onset of the cell death period, and at E 7.5-E8, the middle of the cell death period. Total motoneuron counts a t both E7.5-E8 and E10 (close to the end of cell death period) were si gnificantly decreased compared to controls. These results indicate tha t a treatment that reduces intramuscular nerve branching and synapse f ormation also affects motoneuron survival. Furthermore, since removal of PSA in ovo via endo N altered neither the spontaneous embryonic mot ility nor the activation pattern of motoneurons or muscles, these expe riments avoid the complication of activity blockade that may alter mot oneuron survival by affecting events other than, or in addition to, in tramuscular nerve branching.