Experience-dependent strengthening of Drosophila neuromuscular junctions.

The genetic analysis of larval neuromuscular junctions (NMJs) of Drosophila has provided detailed insights into molecular mechanisms that control the morphological and physiological development of these glutamatergic synapses. However, because of the chronic defects caused by mutations, a time-resolved analysis of these mechanisms and their functional relationships has been difficult so far. In this study we provide a first temporal map of some of the molecular and cellular key processes, which are triggered in wild-type animals by natural larval locomotor activity and then mediate experience-dependent strengthening of larval NMJs.

Differential regulation of active zone density during long-term strengthening of Drosophila neuromuscular junctions.

In this study we established a transgenic Ca2+ imaging technique in Drosophila that enabled us to target the Ca2+ sensor protein yellow Cameleon-2 specifically to larval neurons. This noninvasive method allowed us to measure evoked Ca2+ signals in presynaptic terminals of larval neuromuscular junctions (NMJs). We combined transgenic Ca2+ imaging with electrophysiological recordings and morphological examinations of larval NMJs to analyze the mechanisms underlying persistently enhanced evoked vesicle release in two independent mutants.

The postsynaptic glutamate receptor subunit DGluR-IIA mediates long-term plasticity in Drosophila.

The developing neuromuscular junctions (NMJs) of Drosophila larvae can undergo long-term strengthening of signal transmission, a process that has been shown recently to involve local subsynaptic protein synthesis and that is associated with an elevated synaptic accumulation of the postsynaptic glutamate receptor subunit DGluR-IIA. To analyze the role of altered postsynaptic glutamate receptor expression during this form of genetically induced junctional plasticity, we manipulated the expression levels of two so far-described postsynaptic receptor subunit genes, dglur-IIA and dglur-IIB, in wild-type animals and plasticity mutants. Here we show that elevated synaptic expression of DGluR-IIA, which was achieved by direct transgenic overexpression, by genetically increased subsynaptic protein synthesis, or by a reduced dglur-IIB gene copy number, results in an increased recruitment of active zones, a corresponding enhancement in the strength of junctional signal transmission, and a correlated addition of boutons to the NMJ.