Ultrastructural observations on synapse elimination in neonatal rabbit skeletal muscle.

Electron microscopic techniques were used to investigate two main questions about mammalian neuromuscular development. One, does neonatal synapse elimination proceed by the degeneration of synaptic terminals and preterminal axons, or are the terminals retracted into the parent axon, in a process analogous to the resorption of axonal growth cones? Two, is there any discernible relationship between the elimination of supernumerary synapses and the myelination of preterminal axons? Examination of several hundred sections through endplates fixed at the peak time of synapse elimination revealed no signs of degeneration. This result is not consistent with the proposal that the major mechanism of synapse elimination is terminal degeneration, according to calculations based on the time course of terminal degeneration following neonatal nerve transection. Serial and semi-serial reconstruction of terminals and preterminal axons suggest that myelination of intramuscular axons lags behind synapse elimination and that elimination can proceed while axons bear an immature relationship to Schwann cells. In addition, reconstruction of serial sections through neonatal synapses revealed that their three-dimensional configuration is more complex than that of mature neuromuscular synapses; this feature may be indicative of a dynamic relationship between nerve and muscle at early stages.