Modulation of neuronal activity in the Drosophila mushroom body by DopEcR, a unique dual receptor for ecdysone and dopamine

Abstract

G-protein-coupled receptors (GPCRs) for steroid hormones mediate unconventional steroid signaling and play a significant role in the rapid actions of steroids in a variety of biological processes, including those in the nervous system. However, the effects of these GPCRs on overall neuronal activity remain largely elusive. Drosophila DopEcR is a GPCR that responds to both ecdysone (the major steroid hormone in insects) and dopamine, regulating multiple second messenger systems. Recent studies have revealed that DopEcR is preferentially expressed in the nervous system and involved in behavioral regulation. Here we utilized the bioluminescent Ca2+-indicator GFP-aequorin to monitor the nicotine-induced Ca2+-response within the mushroom bodies (MB), a higher-order brain center in flies, and examined how DopEcR modulates these Ca2+-dynamics. Our results show that in DopEcR knockdown flies, the nicotine-induced Ca2+-response in the MB was significantly enhanced selectively in the medial lobes. We then reveal that application of DopEcR's ligands, ecdysone and dopamine, had different effects on nicotine-induced Ca2+-responses in the MB: ecdysone enhanced activity in the calyx and cell body region in a DopEcR-dependent manner, whereas dopamine reduced activity in the medial lobes independently of DopEcR. Finally, we show that flies with reduced DopEcR function in the MB display decreased locomotor activity. This behavioral phenotype of DopEcR-deficient flies may be partly due to their enhanced MB activity, since the MB have been implicated in the suppression of locomotor activity. Overall, these data suggest that DopEcR is involved in region-specific modulation of Ca2+ dynamics within the MB, which may play a role in behavioral modulation.