From plaque to pretzel: Fold formation and acetylcholine receptor loss at the developing neuromuscular junction

Although there has been progress in understanding the initial steps in the formation of synapses, less is known about their subsequent maturation (San es and Lichtman, 1999). Two alterations on the postsynaptic side of the mam malian neuromuscular junction occur during early postnatal life: acetylchol ine receptors (AChRs) disappear from parts of the developing junction as al l but one axonal inputs are removed, and the topography of the postsynaptic membrane becomes more complicated as gutters and folds are established. We have studied the maturation of the AChR distribution and postsynaptic topo graphy simultaneously by imaging labeled AChRs at the mouse neuromuscular j unction in a new way, using reflected light confocal microscopy. At birth p ostsynaptic receptors were localized in irregular patches within a spoon-sh aped plaque. Beginning several days later, receptor regions within a single endplate were divided into differentiated and less organized compartments. Folds generally oriented orthogonal to the long axis of the muscle fiber w ere seen in developing gutters, although the orientation of the gutters see med to be imposed by the branching pattern of the nerve. Eventually, superf icial regions lacking AChR labeling were apparent in all junctions. In junc tions denervated in the neonatal period both gutter formation and the disap pearance of superficial receptors regions were prevented. We suggest that t ension between growing muscle fibers and the relatively inelastic synaptic terminals that adhere to them causes the topographic features of the postsy naptic membrane. This view provides a mechanical explanation for gutters, f olds, and the location of folds at sites of neurotransmitter release.