| dc.description.abstract | Impulse transmission from the axons of motor neurons to the myofibers of our muscles is essential for virtually all aspects of our physical behavior. It ultimately drives our ability to move, to breathe and to eat, amongst other essential activities. The sites where the impulse transmission occur are termed neuromuscular junctions (NMJs). They are similar to the synapses that mediate impulse transmission in the brain, which underlies, for example, mental behavior. Due to our dependence on neuromuscular transmission for essential aspects of our vitality and its relatively convenient availability for experimentation, considerable attention has been given to understanding how the NMJ functions, how it forms during ontogenetic development, how it is affected by disease and how it reforms after injury. Most of these studies have been made in nonhuman vertebrates, where the fundamental mechanisms are highly conserved from lower organisms to humans.
My study concerns mechanisms involved in ontogenetic development of NMJs in the mouse, a common model used by neuromuscular experimentalists. In mouse, each NMJ is formed by the terminal branches of a motor axon. The branches lie in close apposition to a specialized region of the myofiber membrane called the motor endplate. The endplate occupies about 0.1% of the myofiber surface in adult muscles. Synaptic transmission from the axon terminals to the endplate is mediated by molecules of acetylcholine (ACh). As the nerve fires an action potential, when an impulse traveling along a motor axon reaches its terminals at a neuromuscular junction, it evokes the secretion of ACh from the terminals into a narrow crevice between them and the motor endplate. Once secreted, ACh binds to aggregates of acetylcholine receptors (AChR) on the surface of the endplate, triggering an impulse in the myofiber that leads to its contraction. Capping the axon terminals are terminal Schwann cells (tSCs), the third cellular component of neuromuscular junctions. They play supporting, but essential, roles in the NMJ’s activity. Typically, in mammals there is a single endplate on a muscle fiber. In adults, each endplate is innervated by the terminals of a single axon. On the other hand, at birth, there can be terminal branches of as many as 10 or more separate axons making synaptic contact at a single endplate. Several lines of evidence indicate that the terminals of the different axons compete for sole occupation of the endplate and that the elimination of inputs requires communication between the axon terminals and muscle fiber. Although much has been learned about the nature of the communication driving this transition from poly- to single-innervation our understanding is far from complete. Even less well understood is the behavior of the tSCs during the period of synapse elimination. The aim of my study was to determine in detail the characteristics of tSCs during this period with an eye toward learning whether the tSCs play a direct role in the process. | en |
