Excitation-contraction coupling and its relation to synaptic dysfunction in Drosophila

Abstract

The Drosophila neuromuscular system is widely used to characterize synaptic development and function. However, little is known about how specific synaptic deficits alter neuromuscular transduction and muscle contractility that ultimately dictate behavioural output. Here we develop a system for detailed characterization of excitation-contraction coupling at Drosophila larval NMJs and demonstrate how specific synaptic and neuronal manipulations disrupt muscle contractility. Muscle contraction force increases with motoneuron stimulation frequency and duration, showing considerable plasticity between 5-40 Hz, while saturating above 50 Hz. Temperature is negatively correlated with muscle performance and enhanced at lower temperatures. A screen for modulators of muscle contractility led to the identification and characterization of the molecular and cellular pathway by which a specific FMRFa peptide, TPAEDFMRFa, increases muscle performance. These findings indicate Drosophila NMJs provide a robust system to relate synaptic dysfunction to alterations in excitation-contraction coupling.