The Drosophila larval neuromuscular system is relatively simple, containing only 32 motor neurons in each abdominal hemisegment, and its neuromuscular junctions (NMJs) have been studied extensively. NMJ synapses exhibit developmental and functional plasticity while displaying stereotyped connectivity. Drosophila Type I NMJ synapses are glutamatergic, while the vertebrate NMJ uses acetylcholine as its primary neurotransmitter. The larval NMJ synapses use ionotropic glutamate receptors (GluRs) that are homologous to AMPA-type GluRs in the mammalian brain, and they have postsynaptic scaffolds that resemble those found in mammalian postsynaptic densities. These features make the Drosophila neuromuscular system an excellent genetic model for the study of excitatory synapses in the mammalian central nervous system. The first section of the review presents an overview of NMJ development. The second section describes genes that regulate NMJ development, including: (1) genes that positively and negatively regulate growth of the NMJ, (2) genes required for maintenance of NMJ bouton structure, (3) genes that modulate neuronal activity and alter NMJ growth, (4) genes involved in transsynaptic signaling at the NMJ. The third section describes genes that regulate acute plasticity, focusing on translational regulatory mechanisms. As this review is intended for a developmental biology audience, it does not cover NMJ electrophysiology in detail, and does not review genes for which mutations produce only electrophysiological but no structural phenotypes.
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