MUCH OF OUR UNDERSTANDING of the principles that govern chemical synapses in the brain is based on studies of synapses formed by motor neurons on skeletal muscle cells. The landmark work of Bernard Katz and his colleagues over three decades beginning in 1950 defined the basic parameters of synaptic transmission and opened the door to modern molecular analyses of synaptic function. Therefore, before we examine the complexities of synapses in the central nervous system, we will examine the basic features of chemical synaptic transmission at the simpler nerve-muscle synapse.
The early studies capitalized on several experimental advantages offered by nerve-muscle preparations of various species. Muscles and attached motor axons are easy to dissect and maintain for several hours in vitro. Muscle cells are large enough to be penetrated with two or more fine-tipped microelectrodes, enabling precise analyses of synaptic potentials and underlying ionic currents. In most species, innervation is restricted to one site, the motor end-plate, and in adult animals that site is innervated by only one motor axon. In contrast, central neurons receive many convergent inputs that are distributed throughout the dendritic arbor and the soma, and thus the impact of single inputs is more difficult to discern.
Most important, the chemical transmitter that mediates synaptic transmission between nerve and muscle, acetylcholine (ACh), was identified early in the 20th century. We now know that signaling at the nerve-muscle synapse involves a relatively simple mechanism: Neurotransmitter released from the presynaptic nerve binds to a single type of receptor in the postsynaptic membrane, the nicotinic ACh receptor.1 Binding of transmitter to the receptor directly opens an ion channel; both the receptor and channel are components of the same macromolecule. Synthetic and natural agents that activate or inhibit nicotinic ACh receptors have proven useful in analyzing not only the ACh receptors in muscle, but also cholinergic synapses in peripheral ganglia and in the brain. Moreover, such ligands can be useful therapeutic agents, including the treatment of inherited and acquired neurological diseases resulting from alterations in ACh receptor function or genetic mutations.
The Neuromuscular Junction Has Specialized Presynaptic and Postsynaptic Structures
As the motor axon approaches the end-plate, the site of contact between nerve and muscle (also known as the neuromuscular junction), it loses its myelin sheath and divides into several fine branches. At their ends, these fine branches form multiple expansions or varicosities called synaptic boutons (Figure 12–1) from which the motor axon releases its transmitter. Although myelin ends some distance from the sites of transmitter release, Schwann cells cover and partially enwrap the nerve terminal. A terminal “arbor” defines the area of the motor end-plate. In different species, end-plates range from compact elliptical structures about 20 μm across to linear arrays more than 100 μm in length.
The neuromuscular junction is an ideal site for studying chemical synaptic ...