Building and modifying diverse synaptic properties: Insights from Drosophila

Neuronal synapses are endowed with tremendous structural, functional, and molecular diversity, honed according to the physiological needs of the circuits in which they are embedded. This diversity, once established in development, can subsequently be further modified by plasticity. It is now widely appreciated that even closely related neurons sharing the same molecular machinery can exhibit remarkable diversity in synaptic structure, function, and plasticity. How such synaptic heterogeneity is achieved is now beginning to be elucidated in a powerful model system, the glutamatergic Drosophila neuromuscular junction (NMJ). In this review, we will first discuss recent discoveries about the structural, functional, and genetic diversity at synapses made by two closely related glutamatergic motor neurons at the Drosophila NMJ, MN-Ib and -Is. Next, we detail how inherent synaptic diversity can be subsequently modified by plasticity in response to altered synaptic growth, excess glutamate release, diminished glutamate receptor functionality, and disease. Together, these insights at the Drosophila NMJ have revealed fundamental principles about how closely related synapses are differentially sculpted in development and remodeled through plasticity to ultimately stabilize neural circuit function.