Homeostatic Plasticity of the Mammalian Neuromuscular Junction

The mammalian neuromuscular junction (NMJ) is an ideal preparation to study synaptic plasticity. Its simplicity- one input, one postsynaptic target- allows experimental manipulations and mechanistic analyses that are impossible at more complex synapses. Homeostatic synaptic plasticity attempts to maintain normal function in the face of perturbations in activity. At the NMJ, 3 aspects of activity are sensed to trigger 3 distinct mechanisms that contribute to homeostatic plasticity: Block of presynaptic action potentials triggers increased quantal size secondary to increased release of acetylcholine from vesicles. Simultaneous block of pre- and postsynaptic action potentials triggers an increase in the probability of vesicle release. Block of acetylcholine binding to acetylcholine receptors during spontaneous fusion of single vesicles triggers an increase in the number of releasable vesicles as well as increased motoneuron excitability. Understanding how the NMJ responds to perturbations of synaptic activity informs our understanding of its response to diverse neuromuscular diseases.