An examination of the rearrangement in synaptic connections (""""""""synapse elimination"""""""") occurring in neonatal rat and mouse muscles is proposed. The long-term goal is to understand what qualitative and quantitative roles this rearrangement plays in establishing the adult pattern of innervation of muscles. The project has five specific aims. (1) To examine the role of synapse elimination in the creation of motor units composed of muscle fibers which share the same differentiation or """"""""type"""""""". Recently, immunohistochemistry has been used to show that such fiber types appear during fetal development. We will explore how these early fiber types are arranged into motor units, using glycogen depletion to mark the fibers innervated by a single motor neuron and immunohistochemistry to determine the types of the marked fibers. We expect to be able to show whether synapse elimination has a qualitative role in determining the type composition of motor units. (2) To examine the role of innervation in fiber type differentiation in mammalian fetal muscle. We will use mouse mutants and administration of neurotoxins to produce aneurogenic or paralyzed fetal muscles and analyze the fiber types in these muscles by immunohistochemistry. (3) To examine neonatal muscles for evidence of selectivity in reinnervation. We will determine whether motor neurons show any selectivity in synapse formation for muscle fibers of a particular type or muscle fibers located in a particular muscle position. These experiments should give clues as to how it is that the order present in the innervation of muscle regions and fiber types arises during development. (4) To examine for readjustments in the innervation of muscle fibers occurring after the period of synapse elimination. Experiments have shown that at the end of synapse elimination motor units differ in size and type homogeneity from those in the adult, implying yet further readjustments in muscle innervation. We will examine motor units during the period following synapse elimination to provide further evidence for the occurrence of this rearrangement and its timing. (5) To examine the role of differential neural activity and synapse elimination. We will use stimulation of a portion of the innervation of a muscle to examine whether active axons have any competitive advantage over less active axons in the process of synapse elimination. All of the proposed experiments should further understanding of the development of synaptic connections in muscle.
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