TRANSIENT MUSCLE PARALYSIS IN NEONATAL RATS RENDERS MOTONEURONS SUSCEPTIBLE TO N-METHYL-D-ASPARTATE-INDUCED NEUROTOXICITY

Paralysis of the soleus muscle in newborn rats causes a large proporti on of motoneurons to die by 10 weeks of age. However, all of these neu rons are still present at three to four weeks of age. We have previous ly shown that although nerve injury at five days does not result in an y motoneuron death, it does not render these neurons susceptible to th e toxic effects of the glutamate agonist N-methyl-D-aspartate. Using r etrograde labelling of soleus motoneurons, in this study we show that an increased susceptibility to glutamate also plays a role in the even tual death of those motoneurons which survive for three weeks after in terruption of neuromuscular transmission at birth but die by 10 weeks. Treatment with dizocilpine maleate an antagonist of the N-methyl-D-as partate receptor increased the survival of motoneurons to alpha-bungar otoxin-treated soleus muscles. By 10 weeks of age the size of motoneur ons to alpha-bungarotoxin-treated soleus muscles is smaller than that of controls, but after treatment with dizocilpine maleate the sizes of motoneurons to control and treated muscles are similar. Moreover, onl y 55+/-2.7% of motoneurons to the soleus muscle paralysed at birth wit h alpha-bungarotoxin survive for three weeks after a single injection of N-methyl-D-aspartate since treatment with alpha-bungarotoxin alone causes no loss of neurons at this age. These results provide support f or the proposal that motoneurons deprived of functional interaction wi th their target during a critical period in development, exhibit an in creased sensitivity to the toxic effects of glutamate, and indicate th at such sensitivity may be involved in the long term death of these ne urons.