Many crucial aspects of life, such as movement and breathing, depend on the successful and sustained contraction of skeletal muscle. A critical link in the chain of neurophysiological events in the brain, motor neurons, and muscles that eventually lead to contraction is signal transmission at the neuromuscular junction (NMJ). This synapse, called the endplate, is a microscopic structure on each muscle fibre. It has the essentially simple task of conveying, in a one-on-one fashion, the action potentials fired by the motor neuron onto the muscle fibre membrane. To this end, pre- and postsynaptic specializations exist, which harbour a complex molecular machinery to release and receive, respectively, the neurotransmitter acetylcholine (ACh). The pre- and postsynaptic elements are separated by a narrow synaptic cleft, which contains further structural and functional molecules. In addition, each NMJ is covered by a few perisynaptic Schwann cells (pSCs), which are in close contact with the motor nerve terminal and have trophic and synapse repair-related functions.

In this chapter, the structural and functional aspects of the synaptic compartments of the NMJ will be discussed, as well as their vulnerabilities in myasthenia gravis (MG). The aim is to provide the reader with a background to understand the pathophysiology of this synapse in MG and thereby the mechanisms underlying the muscle weakness of this disorder.