Advances in Real-Time Electrochemical Monitoring of Neurotransmitter Dynamics in Drosophila

Drosophila melanogaster is a genetically tractable model organism with a compact yet functionally rich nervous system, making it ideal for investigating neural mechanisms and modeling neurological diseases. However, its small brain size poses challenges for real-time measurement of neurotransmitter dynamics. Recent advances in electrochemical methodologies, particularly fast-scan cyclic voltammetry (FSCV) and amperometry with carbon fiber microelectrodes, enable high spatiotemporal resolution measurements in vivo. The integration of electrochemistry with optogenetic tools further enhances experimental precision, allowing causal interrogation of neurotransmission. This review summarizes recent advances in electrochemical methodologies for monitoring neurotransmitter dynamics in Drosophila. FSCV has facilitated real-time, chemically selective quantitative analysis of dopamine and serotonin in defined brain regions, providing new insights into their roles in behavior and neurodegeneration, as well as their modulation by antidepressants and ketamine. Amperometry provides complementary capabilities, allowing detection of exocytic release events and quantification of vesicular neurotransmitter content. Amperometric studies have shown that octopamine primarily undergoes partial release at the neuromuscular junction, whereas serotonin in the ventral nerve cord exhibits both partial release and, notably, full vesicular release events. Looking forward, convergence with advanced imaging technologies promises multidimensional views of neurotransmitter signaling and may uncover novel therapeutic targets for neurological diseases. This review highlights key methodological innovations and their applications in Drosophila, underscoring its unique value in bridging molecular neuroscience, behavior, and translational research.